Pub Date : 2025-09-30DOI: 10.1016/j.dci.2025.105479
Ting Luo , Ruo-Xing Yu , Qin-Yang He , Zi-Rou Zhong , Zhuang-Wen Mao , Ming-Zhu Huang , Jie Peng , Yao-Hui Li , Zi-Le Qin , Xu-Ying Kuang , Zi-Xuan Fang , Jian Li , Sheng-Wei Luo
Edwardsiella tarda, a facultative intracellular pathogen, can compromise the health of farmed fish. Nevertheless, the immunometabolic features of red crucian carp (Carassius auratus red var.) after E. tarda 1l-4 infection remains largely understudied. In this investigation, severe tissue injury and aberrant glycogen storage were detected in liver of red crucian carps infected with E. tarda 1l-4, along with the dramatic decline of antioxidant defense. Multiomics approaches indicated that MAPK signaling pathway may assume a dominant role in immunometabolic regulation in red crucian carp. MAPK dysregulation may affect cell cycle and DNA replication, while also disrupting carbon metabolism, amino acid homeostasis and glycerophospholipid biosynthesis, with methylsuccinic acid (MSA) identified as pivotal metabolic indicator. This findings may deepen our understanding of E. tarda-induced immunometabolic responses in red crucian carps and provide practical references for edwardsiellosis management in aquaculture.
迟发爱德华菌是一种兼性细胞内病原体，可危害养殖鱼类的健康。然而，红鲫鱼（Carassius auratus red var.）在感染E. tarda 11 -4后的免疫代谢特征仍未得到充分研究。实验结果表明，感染迟达E. 11 -4后，红鲫肝脏组织损伤严重，糖原储存异常，抗氧化防御能力明显下降。多组学研究表明，MAPK信号通路可能在红鲫免疫代谢调控中起主导作用。MAPK失调可能会影响细胞周期和DNA复制，同时也会破坏碳代谢、氨基酸稳态和甘油磷脂的生物合成，甲基琥珀酸（MSA）被认为是关键的代谢指标。这一发现将加深我们对迟发E.诱导的红鲫免疫代谢反应的认识，并为爱德华氏菌病在水产养殖中的管理提供实用参考。
{"title":"Immunometabolic characteristics in liver of red crucian carp (Carassius auratus red var.) following Edwardsiella tarda 1l-4 infection by multiomics analyses","authors":"Ting Luo , Ruo-Xing Yu , Qin-Yang He , Zi-Rou Zhong , Zhuang-Wen Mao , Ming-Zhu Huang , Jie Peng , Yao-Hui Li , Zi-Le Qin , Xu-Ying Kuang , Zi-Xuan Fang , Jian Li , Sheng-Wei Luo","doi":"10.1016/j.dci.2025.105479","DOIUrl":"10.1016/j.dci.2025.105479","url":null,"abstract":"<div><div><em>Edwardsiella tarda,</em> a facultative intracellular pathogen, can compromise the health of farmed fish. Nevertheless, the immunometabolic features of red crucian carp (<em>Carassius auratus</em> red var.) after <em>E. tarda</em> 1l-4 infection remains largely understudied. In this investigation, severe tissue injury and aberrant glycogen storage were detected in liver of red crucian carps infected with <em>E. tarda</em> 1l-4, along with the dramatic decline of antioxidant defense. Multiomics approaches indicated that MAPK signaling pathway may assume a dominant role in immunometabolic regulation in red crucian carp. MAPK dysregulation may affect cell cycle and DNA replication, while also disrupting carbon metabolism, amino acid homeostasis and glycerophospholipid biosynthesis, with methylsuccinic acid (MSA) identified as pivotal metabolic indicator. This findings may deepen our understanding of <em>E. tarda</em>-induced immunometabolic responses in red crucian carps and provide practical references for edwardsiellosis management in aquaculture.</div></div>","PeriodicalId":11228,"journal":{"name":"Developmental and comparative immunology","volume":"172 ","pages":"Article 105479"},"PeriodicalIF":2.4,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-29DOI: 10.1016/j.dci.2025.105481
Kalodoti Avgousti , Esmeralda Dushku , Anna Spyropoulou , Charalampos Kotzamanidis , Alexandra Staikou , Minas Yiangou
This study explores the probiotic potential, immunomodulatory capacity, and safety of Lactiplantibacillus plantarum and Enterococcus faecalis strains isolated from the intestinal tract of the edible terrestrial snail Cornu aspersum maxima. Although host-microbe interactions are well studied in vertebrates, such research remains limited in invertebrates, particularly snails. To address this gap, 12 lactic acid bacteria strains were isolated and screened for tolerance to the defense mechanisms of snails and probiotic-associated traits, followed by machine learning (ML) predictions of immunomodulatory potential. According to results, 10 strains exhibited high tolerance to the external and internal defense mechanisms of snails (pedal and gastric mucus, gastric juices, low gut pH) in association with increased autoaggregation and hydrophobicity values and were predicted to have 100 % probability of eliciting immunomodulatory activity in vivo. Five strains, the L. plantarum Spp1 and Spp11 and E. faecalis Spp3, Spp8, Spp19, were selected for in vivo evaluation. Strain-specific immune responses were observed, with some strains mainly induced cellular immune responses, such as chemotaxis and phagocytic activity of hemocytes, while others also induced humoral responses. However, safety evaluations revealed that certain E. faecalis strains exhibited antimicrobial resistance or induced inflammatory reactions. Only two strains, the L. plantarum Spp11 and E. faecalis Spp19, were validated as safe and effective immunomodulatory probiotics in vivo. Overall, this study provides a comprehensive comparative analysis of the functionality of probiotic Lactiplantibacillus and Enterococcus strains in snails. These findings advance our understanding of snail-microbe symbiosis, particularly in the context of host-probiotic interactions, and support the use of C. aspersum as a valuable invertebrate model for probiotic research.
{"title":"Revealing probiotic properties of Lactiplantibacillus plantarum and Enterococcus faecalis in Cornu aspersum animal model","authors":"Kalodoti Avgousti , Esmeralda Dushku , Anna Spyropoulou , Charalampos Kotzamanidis , Alexandra Staikou , Minas Yiangou","doi":"10.1016/j.dci.2025.105481","DOIUrl":"10.1016/j.dci.2025.105481","url":null,"abstract":"<div><div>This study explores the probiotic potential, immunomodulatory capacity, and safety of <em>Lactiplantibacillus plantarum</em> and <em>Enterococcus faecalis</em> strains isolated from the intestinal tract of the edible terrestrial snail <em>Cornu aspersum maxima</em>. Although host-microbe interactions are well studied in vertebrates, such research remains limited in invertebrates, particularly snails. To address this gap, 12 lactic acid bacteria strains were isolated and screened for tolerance to the defense mechanisms of snails and probiotic-associated traits, followed by machine learning (ML) predictions of immunomodulatory potential. According to results, 10 strains exhibited high tolerance to the external and internal defense mechanisms of snails (pedal and gastric mucus, gastric juices, low gut pH) in association with increased autoaggregation and hydrophobicity values and were predicted to have 100 % probability of eliciting immunomodulatory activity <em>in vivo</em>. Five strains, the <em>L. plantarum</em> Spp1 and Spp11 and <em>E. faecalis</em> Spp3, Spp8, Spp19, were selected for <em>in vivo</em> evaluation. Strain-specific immune responses were observed, with some strains mainly induced cellular immune responses, such as chemotaxis and phagocytic activity of hemocytes, while others also induced humoral responses. However, safety evaluations revealed that certain <em>E. faecalis</em> strains exhibited antimicrobial resistance or induced inflammatory reactions. Only two strains, the <em>L. plantarum</em> Spp11 and <em>E. faecalis</em> Spp19, were validated as safe and effective immunomodulatory probiotics <em>in vivo</em>. Overall, this study provides a comprehensive comparative analysis of the functionality of probiotic <em>Lactiplantibacillus</em> and <em>Enterococcus</em> strains in snails. These findings advance our understanding of snail-microbe symbiosis, particularly in the context of host-probiotic interactions, and support the use of <em>C. aspersum</em> as a valuable invertebrate model for probiotic research.</div></div>","PeriodicalId":11228,"journal":{"name":"Developmental and comparative immunology","volume":"172 ","pages":"Article 105481"},"PeriodicalIF":2.4,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-29DOI: 10.1016/j.dci.2025.105483
Lilan Xie , Haichuan Li , Qing Guo , Yaoming Li
Interferon-Induced protein 44-Like (IFI44L), a member of the interferon-stimulated genes (ISGs) family, plays a critical role in a variety of biological processes, particularly in antiviral defense and immune regulation. However, the role of human IFI44L in viral replication remains controversial. To further characterize porcine IFI44L (poIFI44L), we cloned poIFI44L for the first time and investigated its role in porcine transmissible gastroenteritis virus (TGEV) replication. The full-length poIFI44L cDNA encodes a 439-amino acid protein, containing an N-terminal TLDc domain and a C-terminal Ras-like GTPase domain. Sequence similarity to orthologs from mouse, hamster, rat, ferret, dog, rabbit, cat, horse, human, monkey, cattle and camel ranged from 48.6 % to 70.2 %. poIFI44L expression was dose-dependently upregulated in PK-15 cells by both poly (I:C) and interferon-alpha (IFNα-2a) treatments. Furthermore, TGEV infection significantly induced poIFI44L expression at both the mRNA and protein levels. Overexpression of poIFI44L in vitro resulted in significantly reduced TGEV N gene mRNA levels, N protein expression, and viral titers in a dose-dependent manner, whereas siRNA-mediated knockdown of poIFI44L enhanced viral replication. Mechanistically, poIFI44L upregulated IFN-β and ISRE promoter activities and upregulated the production of IFN-β and downstream ISGs (ISG56 and ISG60). Collectively, our data suggest that poIFI44L acts as an innate immune effector that suppresses TGEV by activating the IFN-β/ISGs signaling pathway.
{"title":"Porcine IFI44L inhibits transmissible gastroenteritis virus (TGEV) replication by activating IFN-Ⅰ signaling pathway","authors":"Lilan Xie , Haichuan Li , Qing Guo , Yaoming Li","doi":"10.1016/j.dci.2025.105483","DOIUrl":"10.1016/j.dci.2025.105483","url":null,"abstract":"<div><div>Interferon-Induced protein 44-Like (IFI44L), a member of the interferon-stimulated genes (ISGs) family, plays a critical role in a variety of biological processes, particularly in antiviral defense and immune regulation. However, the role of human IFI44L in viral replication remains controversial. To further characterize porcine IFI44L (poIFI44L), we cloned <em>poIFI44L</em> for the first time and investigated its role in porcine transmissible gastroenteritis virus (TGEV) replication. The full-length <em>poIFI44L</em> cDNA encodes a 439-amino acid protein, containing an N-terminal TLDc domain and a C-terminal Ras-like GTPase domain. Sequence similarity to orthologs from mouse, hamster, rat, ferret, dog, rabbit, cat, horse, human, monkey, cattle and camel ranged from 48.6 % to 70.2 %. <em>poIFI44L</em> expression was dose-dependently upregulated in PK-15 cells by both poly (I:C) and interferon-alpha (IFNα-2a) treatments. Furthermore, TGEV infection significantly induced <em>poIFI44L</em> expression at both the mRNA and protein levels. Overexpression of <em>poIFI44L in vitro</em> resulted in significantly reduced TGEV <em>N</em> gene mRNA levels, N protein expression, and viral titers in a dose-dependent manner, whereas siRNA-mediated knockdown of <em>poIFI44L</em> enhanced viral replication. Mechanistically, <em>poIFI44L</em> upregulated IFN-β and ISRE promoter activities and upregulated the production of <em>IFN-β</em> and downstream ISGs (<em>ISG56</em> and <em>ISG60</em>). Collectively, our data suggest that poIFI44L acts as an innate immune effector that suppresses TGEV by activating the IFN-β/ISGs signaling pathway.</div></div>","PeriodicalId":11228,"journal":{"name":"Developmental and comparative immunology","volume":"172 ","pages":"Article 105483"},"PeriodicalIF":2.4,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-26DOI: 10.1016/j.dci.2025.105475
Yawen Yang , Yushuai Xie , Zhaosheng Sun , Zihan Zhang , Chuanguo Cai , Zhitao Qi , Qian Gao
Pentraxins (PTXs) are highly conserved soluble pattern recognition molecules, and play important roles in the innate immunity and autoimmune diseases. In present study, ten PTXs including CRP1, SAP, NPTX1-like, NPTX2a, NPTX2b, NPTXR-like, NPTXRb, PTX3a, PTX3-like and PTX4 were identified from largemouth bass (Micropterus salmoides). These PTXs exhibited high sequence identities with their counterparts of other fish species, and contained conserved motifs and structures of the PTX family, except of PTX3-like. Phylogenetic analysis revealed that these largemouth bass PTXs were closely clustered with their counterparts of other fish species, confirming the correctness of the obtained sequences. Realtime qPCR analysis showed that these PTX genes were widely expressed in all examined tissues, and lipopolysaccharide (LPS), Poly (I:C), and Nocardia seriolae stimulation significantly induced their expressions in head kidney (HK), spleen, gill, and intestine. These results demonstrated the crucial roles of PTXs members in the immune response of largemouth bass against pathogen invasion. To the best of our knowledge, this study represents the first identification of NPTX1, NPTX2b, NPTXRa, NPTXRb, and PTX4 in fish species, as well as the initial documentation of PTXs in largemouth bass.
penttraxins （PTXs）是高度保守的可溶性模式识别分子，在先天免疫和自身免疫性疾病中发挥重要作用。本研究从大口黑鲈（Micropterus salmoides）中鉴定出CRP1、SAP、NPTX1-like、NPTX2a、NPTX2b、NPTXR-like、NPTXRb、PTX3a、PTX3-like和PTX4等10个PTXs。这些PTX与其他鱼类的对应体具有高度的序列一致性，并且包含PTX家族的保守基序和结构，除了ptx3样。系统发育分析表明，这些大口黑鲈的ptx序列与其他鱼类的ptx序列紧密聚类，证实了所获得序列的正确性。real - time qPCR分析显示，这些PTX基因在所有检测组织中广泛表达，脂多糖（LPS）、Poly （I:C）和诺卡菌刺激显著诱导其在头肾（HK）、脾脏、鳃和肠道中的表达。这些结果表明，PTXs成员在大口黑鲈抵御病原体入侵的免疫应答中起着重要作用。据我们所知，本研究首次在鱼类中发现了NPTX1、NPTX2b、NPTXRa、NPTXRb和PTX4，同时也首次在大口黑鲈中发现了PTXs。
{"title":"Pentraxin family members of largemouth bass (Micropterus salmoides): Cloning, characterization and expression responses to LPS, Poly (I:C) and Nocardia seriolae","authors":"Yawen Yang , Yushuai Xie , Zhaosheng Sun , Zihan Zhang , Chuanguo Cai , Zhitao Qi , Qian Gao","doi":"10.1016/j.dci.2025.105475","DOIUrl":"10.1016/j.dci.2025.105475","url":null,"abstract":"<div><div>Pentraxins (PTXs) are highly conserved soluble pattern recognition molecules, and play important roles in the innate immunity and autoimmune diseases. In present study, ten PTXs including CRP1, SAP, NPTX1-like, NPTX2a, NPTX2b, NPTXR-like, NPTXRb, PTX3a, PTX3-like and PTX4 were identified from largemouth bass (<em>Micropterus salmoides</em>). These PTXs exhibited high sequence identities with their counterparts of other fish species, and contained conserved motifs and structures of the PTX family, except of PTX3-like. Phylogenetic analysis revealed that these largemouth bass PTXs were closely clustered with their counterparts of other fish species, confirming the correctness of the obtained sequences. Realtime qPCR analysis showed that these PTX genes were widely expressed in all examined tissues, and lipopolysaccharide (LPS), Poly (I:C), and <em>Nocardia seriolae</em> stimulation significantly induced their expressions in head kidney (HK), spleen, gill, and intestine. These results demonstrated the crucial roles of PTXs members in the immune response of largemouth bass against pathogen invasion. To the best of our knowledge, this study represents the first identification of NPTX1, NPTX2b, NPTXRa, NPTXRb, and PTX4 in fish species, as well as the initial documentation of PTXs in largemouth bass.</div></div>","PeriodicalId":11228,"journal":{"name":"Developmental and comparative immunology","volume":"172 ","pages":"Article 105475"},"PeriodicalIF":2.4,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-23DOI: 10.1016/j.dci.2025.105477
Wenjing Dong , Tianjun Xu , Yuena Sun
Innate immunity constitutes a fundamental defense mechanism in host immunity, wherein myeloid differentiation factor 88 (MyD88) functions as the central adaptor protein in Toll-like receptor (TLR) signaling pathways, orchestrating teleost innate immune responses the nuclear factor-kappa B (NF-κB) pathway. To elucidate the regulatory mechanism of E3 ligase RNF34 (Ring Finger Protein 34) in this signaling cascade, we employed miiuy croaker (Miichthys miiuy) as a model organism and conducted a series of experiments. Luciferase reporter assays demonstrated that RNF34 exerted dose- and time-dependent inhibition on the MyD88-mediated NF-κB signaling pathway. This inhibitory effect persisted under LPS stimulation, confirming RNF34's stable regulatory function. Western blot analysis further revealed that RNF34 negatively regulated MyD88 protein expression, and this regulatory effect was significantly enhanced under LPS stimulation. Mechanistic investigations showed that cycloheximide (CHX) chase assays indicated RNF34 significantly shortened MyD88 protein half-life; treatment with the proteasome inhibitor MG132 completely reversed RNF34-mediated MyD88 degradation; and ubiquitination assays demonstrated that RNF34 substantially enhanced MyD88 ubiquitination levels. These findings collectively indicate that RNF34 promotes MyD88 ubiquitination, leading to its proteasomal degradation and inhibition of NF-κB signaling pathway activation. This study enriches the understanding of RNF34 as a negative immune regulator in miiuy croaker, providing evidence for the regulatory mechanism of the NF-κB signaling pathway in teleosts and offering insights into the precise maintenance of immune homeostasis in teleost fishes.
{"title":"Ring Finger protein 34 negatively regulates MyD88-mediated NF-κB signaling via the ubiquitin-proteasome pathway in miiuy croaker (Miichthys miiuy)","authors":"Wenjing Dong , Tianjun Xu , Yuena Sun","doi":"10.1016/j.dci.2025.105477","DOIUrl":"10.1016/j.dci.2025.105477","url":null,"abstract":"<div><div>Innate immunity constitutes a fundamental defense mechanism in host immunity, wherein myeloid differentiation factor 88 (MyD88) functions as the central adaptor protein in Toll-like receptor (TLR) signaling pathways, orchestrating teleost innate immune responses the nuclear factor-kappa B (NF-κB) pathway. To elucidate the regulatory mechanism of E3 ligase RNF34 (Ring Finger Protein 34) in this signaling cascade, we employed miiuy croaker (<em>Miichthys miiuy</em>) as a model organism and conducted a series of experiments. Luciferase reporter assays demonstrated that RNF34 exerted dose- and time-dependent inhibition on the MyD88-mediated NF-κB signaling pathway. This inhibitory effect persisted under LPS stimulation, confirming RNF34's stable regulatory function. Western blot analysis further revealed that RNF34 negatively regulated MyD88 protein expression, and this regulatory effect was significantly enhanced under LPS stimulation. Mechanistic investigations showed that cycloheximide (CHX) chase assays indicated RNF34 significantly shortened MyD88 protein half-life; treatment with the proteasome inhibitor MG132 completely reversed RNF34-mediated MyD88 degradation; and ubiquitination assays demonstrated that RNF34 substantially enhanced MyD88 ubiquitination levels. These findings collectively indicate that RNF34 promotes MyD88 ubiquitination, leading to its proteasomal degradation and inhibition of NF-κB signaling pathway activation. This study enriches the understanding of RNF34 as a negative immune regulator in miiuy croaker, providing evidence for the regulatory mechanism of the NF-κB signaling pathway in teleosts and offering insights into the precise maintenance of immune homeostasis in teleost fishes.</div></div>","PeriodicalId":11228,"journal":{"name":"Developmental and comparative immunology","volume":"172 ","pages":"Article 105477"},"PeriodicalIF":2.4,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MicroRNAs (miRNAs), a class of small non-coding RNAs critical for post-transcriptional gene regulation, serve as key immune modulators in vertebrates. However, their roles in teleost disease resistance remain underexplored. In the present study, a comprehensive miRNA transcriptome analysis was conducted in Takifugu obscurus under Vibrio harveyi challenge using high-throughput RNA sequencing. Three miRNA libraries (ToCG, ToEG1, and ToEG2) were constructed from kidney tissues of T. obscurus collected at 0 h (non-infected control), 6 h, and 24 h post-infection. Bioinformatics analysis identified 1093 miRNAs, including 195 novel miRNAs, and revealed 175 differentially expressed miRNAs (DEmiRNAs) across infection timepoints. Validation experiments via quantitative real-time PCR confirmed the expression patterns of 16 randomly selected DEmiRNAs, demonstrating high consistency with sequencing data. Functional enrichment analysis of DEmiRNAs highlighted significant associations with immune regulatory pathways, including mitogen-activated protein kinase signaling, Forkhead box O signaling, erythroblastic leukemia viral oncogene homolog signaling, and endocytosis pathways. Notably, several DEmiRNAs exhibited temporal expression patterns, suggesting stage-specific immunoregulatory functions during bacterial pathogenesis. This study suggests a potential miRNA regulatory network in T. obscurus during V. harveyi infection, providing crucial insights into conserved and species-specific miRNA-mediated immune mechanisms in teleosts.
{"title":"Integrated analysis of microRNA expression profiles in Takifugu obscurus kidney following Vibrio harveyi challenge","authors":"Rui Shen, Hao Wu, Qian-Hui Yuan, Zhe Zhao, Ying Huang","doi":"10.1016/j.dci.2025.105478","DOIUrl":"10.1016/j.dci.2025.105478","url":null,"abstract":"<div><div>MicroRNAs (miRNAs), a class of small non-coding RNAs critical for post-transcriptional gene regulation, serve as key immune modulators in vertebrates. However, their roles in teleost disease resistance remain underexplored. In the present study, a comprehensive miRNA transcriptome analysis was conducted in <em>Takifugu obscurus</em> under <em>Vibrio harveyi</em> challenge using high-throughput RNA sequencing. Three miRNA libraries (ToCG, ToEG1, and ToEG2) were constructed from kidney tissues of <em>T</em>. <em>obscurus</em> collected at 0 h (non-infected control), 6 h, and 24 h post-infection. Bioinformatics analysis identified 1093 miRNAs, including 195 novel miRNAs, and revealed 175 differentially expressed miRNAs (DEmiRNAs) across infection timepoints. Validation experiments via quantitative real-time PCR confirmed the expression patterns of 16 randomly selected DEmiRNAs, demonstrating high consistency with sequencing data. Functional enrichment analysis of DEmiRNAs highlighted significant associations with immune regulatory pathways, including mitogen-activated protein kinase signaling, Forkhead box O signaling, erythroblastic leukemia viral oncogene homolog signaling, and endocytosis pathways. Notably, several DEmiRNAs exhibited temporal expression patterns, suggesting stage-specific immunoregulatory functions during bacterial pathogenesis. This study suggests a potential miRNA regulatory network in <em>T. obscurus</em> during <em>V. harveyi</em> infection, providing crucial insights into conserved and species-specific miRNA-mediated immune mechanisms in teleosts.</div></div>","PeriodicalId":11228,"journal":{"name":"Developmental and comparative immunology","volume":"172 ","pages":"Article 105478"},"PeriodicalIF":2.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145120084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-21DOI: 10.1016/j.dci.2025.105476
Yue Kong , Saikun Pan , Shengjun Wu
β-glucan, a bioactive polysaccharide derived from fungi, yeast, grains, and algae, has become a versatile element in aquaculture feeding. This review thoroughly examines the structural differences, extraction techniques, and purification methods of β-glucans, correlating these characteristics with their biological effectiveness. Particular attention is given to their antioxidant, immunomodulatory, antibacterial, and hypolipidemic properties, along with their integration into functional diets to enhance aquatic animal performance. β-glucan supplementation has demonstrated effectiveness in enhancing development, augmenting disease resistance, and fortifying stress tolerance in many aquatic species by altering innate immunity, oxidative equilibrium, and metabolic functions. The fundamental mechanisms, encompassing receptor-mediated signaling pathways and dose-dependent responses, are meticulously examined. Furthermore, issues pertaining to delivery techniques, structural integrity, and practical use are examined. This investigation underscores β-glucan as a viable and sustainable substitute for antibiotics in enhancing aquaculture health and productivity.
{"title":"Advances in the use of dietary β-glucan in aquaculture: Structural insights, immunological benefits, and feed applications","authors":"Yue Kong , Saikun Pan , Shengjun Wu","doi":"10.1016/j.dci.2025.105476","DOIUrl":"10.1016/j.dci.2025.105476","url":null,"abstract":"<div><div>β-glucan, a bioactive polysaccharide derived from fungi, yeast, grains, and algae, has become a versatile element in aquaculture feeding. This review thoroughly examines the structural differences, extraction techniques, and purification methods of β-glucans, correlating these characteristics with their biological effectiveness. Particular attention is given to their antioxidant, immunomodulatory, antibacterial, and hypolipidemic properties, along with their integration into functional diets to enhance aquatic animal performance. β-glucan supplementation has demonstrated effectiveness in enhancing development, augmenting disease resistance, and fortifying stress tolerance in many aquatic species by altering innate immunity, oxidative equilibrium, and metabolic functions. The fundamental mechanisms, encompassing receptor-mediated signaling pathways and dose-dependent responses, are meticulously examined. Furthermore, issues pertaining to delivery techniques, structural integrity, and practical use are examined. This investigation underscores β-glucan as a viable and sustainable substitute for antibiotics in enhancing aquaculture health and productivity.</div></div>","PeriodicalId":11228,"journal":{"name":"Developmental and comparative immunology","volume":"172 ","pages":"Article 105476"},"PeriodicalIF":2.4,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-20DOI: 10.1016/j.dci.2025.105474
Samira Christin Görig , Yeliz Gün , Dimitri Leonid Lindenwald , Jochen Meens , Hans-Joachim Schuberth , Bernd Lepenies
Pattern recognition receptors (PRRs) are an essential component of the innate immune system. Myeloid C-type-lectin receptors (CLRs) serve as PRRs and play a crucial role in pathogen recognition. While the role of CLRs has been mainly studied in mice and humans, their function in cattle is poorly understood. To address this gap, we generated a novel bovine CLR-hFc fusion protein library, enabling high-throughput screening of bovine CLR/pathogen interactions.
The functionality of the bovine CLR-hFc fusion proteins was validated with known CLR ligands using ELISA- and flow cytometry-based binding assays, by comparison of bovine CLRs with their murine, ovine and human orthologues. In a proof-of-principle pathogen binding study, we assessed CLR binding to Pasteurella (P.) multocida, a Gram-negative bacterial pathogen causing hemorrhagic septicemia in cattle. The bovine CLR myeloid inhibitory C-type lectin (MICL, Clec12A) was identified as a potential receptor for P. multocida, as it exhibited significant binding in flow cytometry binding assays. Cross-species analysis confirmed that murine and ovine MICL also binds P. multocida, suggesting an evolutionarily conserved recognition.
To explore MICL-dependent innate responses to P. multocida-derived factors, cytokine assays were performed using dendritic cells (DCs) from wild-type (WT) and MICL-deficient (MICL−/−) mice. MICL−/− DCs produced higher levels of IL-6 and IL-12 upon stimulation with heat-killed P. multocida, suggesting a role for MICL in the down-modulation of innate responses.
The results highlight MICL as a receptor in the recognition of P. multocida and demonstrate the utility of the generated bovine CLR-hFc fusion protein library for pathogen screening.
{"title":"Screening for C-type lectin receptor (CLR)/bacteria interactions using a bovine CLR-Fc fusion protein library reveals recognition of Pasteurella multocida B:2 by MICL","authors":"Samira Christin Görig , Yeliz Gün , Dimitri Leonid Lindenwald , Jochen Meens , Hans-Joachim Schuberth , Bernd Lepenies","doi":"10.1016/j.dci.2025.105474","DOIUrl":"10.1016/j.dci.2025.105474","url":null,"abstract":"<div><div>Pattern recognition receptors (PRRs) are an essential component of the innate immune system. Myeloid C-type-lectin receptors (CLRs) serve as PRRs and play a crucial role in pathogen recognition. While the role of CLRs has been mainly studied in mice and humans, their function in cattle is poorly understood. To address this gap, we generated a novel bovine CLR-hFc fusion protein library, enabling high-throughput screening of bovine CLR/pathogen interactions.</div><div>The functionality of the bovine CLR-hFc fusion proteins was validated with known CLR ligands using ELISA- and flow cytometry-based binding assays, by comparison of bovine CLRs with their murine, ovine and human orthologues. In a proof-of-principle pathogen binding study, we assessed CLR binding to <em>Pasteurella (P.) multocida,</em> a Gram-negative bacterial pathogen causing hemorrhagic septicemia in cattle. The bovine CLR myeloid inhibitory C-type lectin (MICL, Clec12A) was identified as a potential receptor for <em>P. multocida</em>, as it exhibited significant binding in flow cytometry binding assays. Cross-species analysis confirmed that murine and ovine MICL also binds <em>P. multocida</em>, suggesting an evolutionarily conserved recognition.</div><div>To explore MICL-dependent innate responses to <em>P. multocida</em>-derived factors, cytokine assays were performed using dendritic cells (DCs) from wild-type (WT) and MICL-deficient (MICL<sup>−/−</sup>) mice. MICL<sup>−/−</sup> DCs produced higher levels of IL-6 and IL-12 upon stimulation with heat-killed <em>P. multocida</em>, suggesting a role for MICL in the down-modulation of innate responses.</div><div>The results highlight MICL as a receptor in the recognition of <em>P. multocida</em> and demonstrate the utility of the generated bovine CLR-hFc fusion protein library for pathogen screening.</div></div>","PeriodicalId":11228,"journal":{"name":"Developmental and comparative immunology","volume":"172 ","pages":"Article 105474"},"PeriodicalIF":2.4,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-19DOI: 10.1016/j.dci.2025.105470
Nurnabi Ahmed , Babul Chandra Roy , Amitav Biswas , Md Rajiur Rahaman Rabbi , Md Mahfuzur Rahman Sajib , Mohammad Manjurul Hasan , Hiranmoy Biswas , MD Hasanuzzaman Talukder
Haemonchus contortus is a major threat to small ruminant health and productivity. Although early Th2 cytokine and transcription factor expression confers protection in naturally resistant breeds, the immune basis of resistance in Black Bengal goats (BBG) remains unexplored. We compare early PBMC-mediated cytokine and transcriptional responses and their direct effects on larval motility between naive and primed BBG kids during the first seven days of infection. Kids were primed with 2000 L3 weekly for four weeks or left naive, then challenged with 10,000 L3. Two kids per group were sacrificed on each time point. Whole blood was collected pre-mortem for differential counts and PBMC isolation, while abomasal mucosa and draining LN were harvested for histology and RNA extraction. Primed kids exhibited a 58 % reduction in abomasal L4 burden by day 7, elevated PCV (p < 0.05), and a threefold greater increase in LN weight compared to naive kids. Histopathology revealed significantly enhanced eosinophil and neutrophil infiltration in abomasal mucosa of primed kids. Cytokine and gene expression assay showed early upregulation of Interleukin (IL)-4, IL-5, IL-13, IL-33, MCP-1, CXCL-1, TLR-2, and GAL-14 (p < 0.05). In vitro, co-culture with primed PBMCs reduced L3 motility compared to naive PBMCs (p < 0.01) and L3 pretreated with primed PBMCs resulted in a 60 % reduction in fecal egg counts by week 5 (p < 0.001). This is the first study to integrate daily PBMC transcriptomics with functional motility and infectivity assays in BBGs. The findings identify novel biomarkers, inform selective breeding and immunoprophylactic strategies for sustainable parasite control.
{"title":"Peripheral blood mononuclear cell-driven cytokine and transcription factors induction confers resistance to Haemonchus contortus in Black Bengal goats","authors":"Nurnabi Ahmed , Babul Chandra Roy , Amitav Biswas , Md Rajiur Rahaman Rabbi , Md Mahfuzur Rahman Sajib , Mohammad Manjurul Hasan , Hiranmoy Biswas , MD Hasanuzzaman Talukder","doi":"10.1016/j.dci.2025.105470","DOIUrl":"10.1016/j.dci.2025.105470","url":null,"abstract":"<div><div><em>Haemonchus contortus</em> is a major threat to small ruminant health and productivity. Although early Th2 cytokine and transcription factor expression confers protection in naturally resistant breeds, the immune basis of resistance in Black Bengal goats (BBG) remains unexplored. We compare early PBMC-mediated cytokine and transcriptional responses and their direct effects on larval motility between naive and primed BBG kids during the first seven days of infection. Kids were primed with 2000 L<sub>3</sub> weekly for four weeks or left naive, then challenged with 10,000 L<sub>3</sub>. Two kids per group were sacrificed on each time point. Whole blood was collected pre-mortem for differential counts and PBMC isolation, while abomasal mucosa and draining LN were harvested for histology and RNA extraction. Primed kids exhibited a 58 % reduction in abomasal L<sub>4</sub> burden by day 7, elevated PCV (<em>p <</em> 0.05), and a threefold greater increase in LN weight compared to naive kids. Histopathology revealed significantly enhanced eosinophil and neutrophil infiltration in abomasal mucosa of primed kids. Cytokine and gene expression assay showed early upregulation of Interleukin (IL)-4, IL-5, IL-13, IL-33, MCP-1, CXCL-1, TLR-2, and GAL-14 (p < 0.05). <em>In vitro</em>, co-culture with primed PBMCs reduced L<sub>3</sub> motility compared to naive PBMCs (p < 0.01) and L<sub>3</sub> pretreated with primed PBMCs resulted in a 60 % reduction in fecal egg counts by week 5 (p < 0.001). This is the first study to integrate daily PBMC transcriptomics with functional motility and infectivity assays in BBGs. The findings identify novel biomarkers, inform selective breeding and immunoprophylactic strategies for sustainable parasite control.</div></div>","PeriodicalId":11228,"journal":{"name":"Developmental and comparative immunology","volume":"172 ","pages":"Article 105470"},"PeriodicalIF":2.4,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-18DOI: 10.1016/j.dci.2025.105469
Yang Lei , Weiheng Shi , Yanxi Guo , Yuqing Lin , Jianmin Ye , Liting Wu
Complement receptor 3 (CR3), also known as integrin αMβ2, CD11b/CD18, or Mac-1, is a heterodimeric leukocyte-specific integrin composed of the αM (CD11b) and β2 (CD18) subunits. To elucidate the role of CR3 in immunity in Nile tilapia (Oreochromis niloticus), we cloned and characterized the αM (OnCD11b) and β2 (OnCD18) subunits and investigated their functions both in vivo and in vitro. Sequence analysis revealed that OnCD11b contains a 3378-bp open reading frame (ORF) encoding a protein of 1128 amino acids (124.7 kDa), while OnCD18 comprises a 2337-bp ORF encoding 778 amino acids (85.7 kDa). Structural alignment demonstrated high degree of conservation in the von Willebrand factor type A (vWFA) domains of both subunits, with significant homology to CD11b and CD18 orthologs across species. Phylogenetic analysis confirmed that OnCD11b and OnCD18 cluster within the teleost-specific CD11b and CD18 clades, respectively. Tissue-specific expression profiling indicated predominant expression of OnCD11b in the head kidney and OnCD18 in the spleen. Both subunits were significantly upregulated in these tissues following challenges with Streptococcus agalactiae (S. agalactiae) and Aeromonas hydrophila (A. hydrophila), suggesting their involvement in pathogen-induced immune responses. In vitro functional assays demonstrated that the recombinant vWFA domains of OnCD11b and OnCD18 exhibited specific binding capacity to S. agalactiae, A. hydrophila, and lipopolysaccharide, highlighting their role as pattern recognition receptors. Crucially, in vivo knockdown of OnCD11b or OnCD18 resulted in a significant increase in bacterial load in tilapia tissues following S. agalactiae infection, underscoring their essential role in host defense. These findings collectively demonstrate that OnCD11b and OnCD18 are pivotal components of the immune system in Nile tilapia, facilitating bacterial clearance through direct pathogen recognition pathway. This study provides new insights into the evolutionarily conserved mechanisms of CR3-mediated immunity and potential therapeutic targets for bacterial infections in aquaculture species.
{"title":"Functional characterization of complement receptor 3 (CR3) in Nile tilapia (Oreochromis niloticus): Insights into CD11b/CD18-mediated immunity against bacterial infections","authors":"Yang Lei , Weiheng Shi , Yanxi Guo , Yuqing Lin , Jianmin Ye , Liting Wu","doi":"10.1016/j.dci.2025.105469","DOIUrl":"10.1016/j.dci.2025.105469","url":null,"abstract":"<div><div>Complement receptor 3 (CR3), also known as integrin αMβ2, CD11b/CD18, or Mac-1, is a heterodimeric leukocyte-specific integrin composed of the αM (CD11b) and β2 (CD18) subunits. To elucidate the role of CR3 in immunity in Nile tilapia (<em>Oreochromis niloticus</em>), we cloned and characterized the αM (<em>On</em>CD11b) and β2 (<em>On</em>CD18) subunits and investigated their functions both <em>in vivo</em> and <em>in vitro</em>. Sequence analysis revealed that <em>On</em>CD11b contains a 3378-bp open reading frame (ORF) encoding a protein of 1128 amino acids (124.7 kDa), while <em>On</em>CD18 comprises a 2337-bp ORF encoding 778 amino acids (85.7 kDa). Structural alignment demonstrated high degree of conservation in the von Willebrand factor type A (vWFA) domains of both subunits, with significant homology to CD11b and CD18 orthologs across species. Phylogenetic analysis confirmed that <em>On</em>CD11b and <em>On</em>CD18 cluster within the teleost-specific CD11b and CD18 clades, respectively. Tissue-specific expression profiling indicated predominant expression of <em>On</em>CD11b in the head kidney and <em>On</em>CD18 in the spleen. Both subunits were significantly upregulated in these tissues following challenges with <em>Streptococcus agalactiae</em> (<em>S. agalactiae</em>) and <em>Aeromonas hydrophila</em> (<em>A. hydrophila</em>), suggesting their involvement in pathogen-induced immune responses. <em>In vitro</em> functional assays demonstrated that the recombinant vWFA domains of <em>On</em>CD11b and <em>On</em>CD18 exhibited specific binding capacity to <em>S. agalactiae</em>, <em>A. hydrophila</em>, and lipopolysaccharide, highlighting their role as pattern recognition receptors. Crucially, <em>in vivo</em> knockdown of <em>On</em>CD11b or <em>On</em>CD18 resulted in a significant increase in bacterial load in tilapia tissues following <em>S. agalactiae</em> infection, underscoring their essential role in host defense. These findings collectively demonstrate that <em>On</em>CD11b and <em>On</em>CD18 are pivotal components of the immune system in Nile tilapia, facilitating bacterial clearance through direct pathogen recognition pathway. This study provides new insights into the evolutionarily conserved mechanisms of CR3-mediated immunity and potential therapeutic targets for bacterial infections in aquaculture species.</div></div>","PeriodicalId":11228,"journal":{"name":"Developmental and comparative immunology","volume":"172 ","pages":"Article 105469"},"PeriodicalIF":2.4,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145098908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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