Pub Date : 2025-03-01DOI: 10.1016/j.micinf.2024.105435
Dener Lucas Araújo dos Santos , Juliana Santana de Curcio , Evandro Novaes , Célia Maria de Almeida Soares
Copper is an essential metal for cellular processes such as detoxification of reactive oxygen species, oxidative phosphorylation, and iron uptake. However, during infection, the host restricts the bioavailability of this micronutrient to the pathogen as a strategy to combat infection. Recently, we have shown the involvement of miRNAs as an adaptive strategy of P. brasiliensis upon metal deprivation such as iron and zinc. However, their role in copper limitation still needs to be elucidated. Our objective was to characterize the expression profile of miRNAs regulated during copper deprivation in P. brasiliensis and the putative altered processes. Through RNAseq analysis and bioinformatics, we identified 14 differentially expressed miRNAs, two of which putatively regulated oxidative stress response, beta-oxidation, glyoxylate cycle, and cell wall remodeling. Our results suggest that metabolic adaptations carried out by P. brasiliensis in copper deprivation are regulated by miRNAs.
{"title":"miRNAs regulate the metabolic adaptation of Paracoccidioides brasiliensis during copper deprivation","authors":"Dener Lucas Araújo dos Santos , Juliana Santana de Curcio , Evandro Novaes , Célia Maria de Almeida Soares","doi":"10.1016/j.micinf.2024.105435","DOIUrl":"10.1016/j.micinf.2024.105435","url":null,"abstract":"<div><div>Copper is an essential metal for cellular processes such as detoxification of reactive oxygen species, oxidative phosphorylation, and iron uptake. However, during infection, the host restricts the bioavailability of this micronutrient to the pathogen as a strategy to combat infection. Recently, we have shown the involvement of miRNAs as an adaptive strategy of <em>P. brasiliensis</em> upon metal deprivation such as iron and zinc. However, their role in copper limitation still needs to be elucidated. Our objective was to characterize the expression profile of miRNAs regulated during copper deprivation in <em>P. brasiliensis</em> and the putative altered processes. Through RNAseq analysis and bioinformatics, we identified 14 differentially expressed miRNAs, two of which putatively regulated oxidative stress response, beta-oxidation, glyoxylate cycle, and cell wall remodeling. Our results suggest that metabolic adaptations carried out by <em>P</em>. <em>brasiliensis</em> in copper deprivation are regulated by miRNAs.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 3","pages":"Article 105435"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.micinf.2024.105439
Angela Silvano , Javier Sotillo , Marta Cecchi , Alex Loukas , Mireille Ouedraogo , Astrid Parenti , Fabrizio Bruschi , Maria Gabriella Torcia , Valentina D Mangano
Urogenital schistosomiasis caused by Schistosoma haematobium is a major cause of disability in endemic areas. Despite its socio-economic burden, no vaccine exists and the parasite's immunobiology remains underexplored. Genome annotation has revealed over 40 different genes encoding tetraspanins, transmembrane proteins with known immunomodulatory properties in other plathelminthes. This study investigated the role of Sh-TSP-2, Sh-TSP-6 and Sh-TSP-23, which are expressed in the parasite's tegument and extracellular vesicles (EVs). Immature dendritic cells (DCs) from unexposed healthy donors were stimulated with these proteins to evaluate maturation maker expression and cytokine production. Also, pre-activated T CD4+ cells were stimulated with the DCs supernatant to assess cytokine gene expression. Sh-TSP-2 and Sh-TSP-6 induced maturation markers and cytokine production in DCs: Sh-TSP-2 increased CD80 and CD83 levels and the concentration of both pro-inflammatory (IL-6, TNF) and regulatory (IL-10) cytokines, while Sh-TSP-6 increased the production of IL-6. Moreover, supernatants from Sh-TSP-2 stimulated DCs induced the expression of Th1 (IFNɣ) and regulatory (IL-10) cytokines in CD4+ T cells, while Sh-TSP-6 induced Th2 (IL-4, IL-13) cytokine expression. These results provide evidence that S. haematobium tetraspanins modulate the response of human DCs and CD4+ T cells in vitro, and support Sh-TSP-2 as a promising vaccine candidate.
{"title":"Schistosoma heamatobium tetraspanins TSP-2 and TSP-6 induce Dendritic Cells maturation, cytokine production and T helper cells differentiation in vitro","authors":"Angela Silvano , Javier Sotillo , Marta Cecchi , Alex Loukas , Mireille Ouedraogo , Astrid Parenti , Fabrizio Bruschi , Maria Gabriella Torcia , Valentina D Mangano","doi":"10.1016/j.micinf.2024.105439","DOIUrl":"10.1016/j.micinf.2024.105439","url":null,"abstract":"<div><div>Urogenital schistosomiasis caused by <em>Schistosoma haematobium</em> is a major cause of disability in endemic areas. Despite its socio-economic burden, no vaccine exists and the parasite's immunobiology remains underexplored. Genome annotation has revealed over 40 different genes encoding tetraspanins, transmembrane proteins with known immunomodulatory properties in other plathelminthes. This study investigated the role of <em>Sh</em>-TSP-2, <em>Sh</em>-TSP-6 and <em>Sh</em>-TSP-23, which are expressed in the parasite's tegument and extracellular vesicles (EVs). Immature dendritic cells (DCs) from unexposed healthy donors were stimulated with these proteins to evaluate maturation maker expression and cytokine production. Also, pre-activated T CD4<sup>+</sup> cells were stimulated with the DCs supernatant to assess cytokine gene expression. <em>Sh</em>-TSP-2 and <em>Sh</em>-TSP-6 induced maturation markers and cytokine production in DCs: <em>Sh</em>-TSP-2 increased CD80 and CD83 levels and the concentration of both pro-inflammatory (IL-6, TNF) and regulatory (IL-10) cytokines, while <em>Sh</em>-TSP-6 increased the production of IL-6. Moreover, supernatants from <em>Sh</em>-TSP-2 stimulated DCs induced the expression of Th1 (IFNɣ) and regulatory (IL-10) cytokines in CD4<sup>+</sup> T cells, while <em>Sh-</em>TSP-6 induced Th2 (IL-4, IL-13) cytokine expression. These results provide evidence that <em>S. haematobium</em> tetraspanins modulate the response of human DCs and CD4<sup>+</sup> T cells <em>in vitro,</em> and support <em>Sh</em>-TSP-2 as a promising vaccine candidate.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 3","pages":"Article 105439"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The growing evidence has underscored the significance of interactions between the host and microbiota in respiratory health, presenting a novel perspective on disease management. Yet, comprehension of the respiratory microbiome shifts before and after anti-tuberculosis treatment is limited. This study compares respiratory microbiome profiles in untreated tuberculosis (UTB) and completed TB treatment (CTB) cases with healthy controls, using 16S rRNA sequencing on sputum samples. Significant reduction in sputum microbial alpha diversity was observed in both TB groups when compared to healthy controls (P < 0.05). Beta diversity analysis showed distinct clustering (P < 0.05). Linear discriminant analysis revealed an abundance of potentially pathogenic bacterial genera like Haemophilus, Pseudomonas, and Mycobacterium in the UTB group, while Streptococcus, Rothia, and Neisseria dominated in CTB samples. Healthy sputum microbiomes were enriched with Prevotella, Fusobacterium, Porphyromonadaceae_unclassified,andPeptostreptococcus. Moreover, predicted bacterial functional pathways showed significant differences among the three groups, mainly related to nutrient metabolism.
These findings indicated significant microbial dysbiosis in sputum samples recovered from patients with pulmonary TB with an elevated presence of potentially pathogenic bacteria, depletion of beneficial genera, and downregulation of several essential metabolic pathways. Further exploration of respiratory microbiome-based diagnostic biomarkers and their role in targeted treatment strategies in tuberculosis is warranted.
{"title":"The impact of anti-tuberculosis treatment on respiratory tract microbiome in pulmonary tuberculosis","authors":"Druti Hazra , Kiran Chawla , Fayaz S.M. , Vitali Sintchenko , Rahul Magazine , Elena Martinez , Akhilesh Pandey","doi":"10.1016/j.micinf.2024.105432","DOIUrl":"10.1016/j.micinf.2024.105432","url":null,"abstract":"<div><div>The growing evidence has underscored the significance of interactions between the host and microbiota in respiratory health, presenting a novel perspective on disease management. Yet, comprehension of the respiratory microbiome shifts before and after anti-tuberculosis treatment is limited. This study compares respiratory microbiome profiles in untreated tuberculosis (UTB) and completed TB treatment (CTB) cases with healthy controls, using 16S rRNA sequencing on sputum samples. Significant reduction in sputum microbial alpha diversity was observed in both TB groups when compared to healthy controls (P < 0.05). Beta diversity analysis showed distinct clustering (P < 0.05). Linear discriminant analysis revealed an abundance of potentially pathogenic bacterial genera like <em>Haemophilus, Pseudomonas</em>, and <em>Mycobacterium</em> in the UTB group, while <em>Streptococcus, Rothia</em>, and <em>Neisseria</em> dominated in CTB samples. Healthy sputum microbiomes were enriched with <em>Prevotella, Fusobacterium, Porphyromonadaceae_unclassified,</em> <em>and</em> <em>Peptostreptococcus</em>. Moreover, predicted bacterial functional pathways showed significant differences among the three groups, mainly related to nutrient metabolism.</div><div>These findings indicated significant microbial dysbiosis in sputum samples recovered from patients with pulmonary TB with an elevated presence of potentially pathogenic bacteria, depletion of beneficial genera, and downregulation of several essential metabolic pathways. Further exploration of respiratory microbiome-based diagnostic biomarkers and their role in targeted treatment strategies in tuberculosis is warranted.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 3","pages":"Article 105432"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142469726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.micinf.2024.105462
Eun-Jin Ha , Seung-Min Hong , Kang-Seuk Choi , Hyuk-Joon Kwon
The O1 and O2 serogroups of avian pathogenic E. coli (APEC) and human extraintestinal pathogenic E. coli (huExPEC) are closely related, but their evolutionary relationships need to be further elucidated. This study classified nineteen O1 and O2 APEC into rpoB sequence types (RSTs) and compared them with reference huExPEC using molecular prophage typing, virulence and antibiotic resistance gene profiling, and comparative genomics. Most O1:K1 and O2:K1 APEC (73.7 %) were classified as RST46-1 and RST47-9. RST47-9 is unique to Korean O1 APEC and likely derives from RST46-1 APEC. The six APEC showed high genome coverage/identity with the Korean RST46-1 huExPEC. Based on RST network and comparative genomics, we hypothesized that the O1 antigen first appeared in RST19-1 and O2 in RST24-1 E. coli in humans. Then, O1 and O2-antigen horizontally transferred to human RST46-1, where a unique K1 capsule (K1-cps) first appeared. The Korean APEC and huExPEC share evolutionary CRISPR spacers but differ in molecular antibiograms and prophage contents. Thus, RST46-1 huExPEC transmitted and evolved in poultry. The zoonotic risks remain unknown, but the substantial virulence of the RST46-1 APEC indicates that the reverse zoonotic risk of huExPEC in poultry is alarming.
{"title":"Evolution and zoonotic risk of O1:K1 and O2:K1 avian pathogenic Escherichia coli","authors":"Eun-Jin Ha , Seung-Min Hong , Kang-Seuk Choi , Hyuk-Joon Kwon","doi":"10.1016/j.micinf.2024.105462","DOIUrl":"10.1016/j.micinf.2024.105462","url":null,"abstract":"<div><div>The O1 and O2 serogroups of avian pathogenic <em>E. coli</em> (APEC) and human extraintestinal pathogenic <em>E. coli</em> (huExPEC) are closely related, but their evolutionary relationships need to be further elucidated. This study classified nineteen O1 and O2 APEC into <em>rpoB</em> sequence types (RSTs) and compared them with reference huExPEC using molecular prophage typing, virulence and antibiotic resistance gene profiling, and comparative genomics. Most O1:K1 and O2:K1 APEC (73.7 %) were classified as RST46-1 and RST47-9. RST47-9 is unique to Korean O1 APEC and likely derives from RST46-1 APEC. The six APEC showed high genome coverage/identity with the Korean RST46-1 huExPEC. Based on RST network and comparative genomics, we hypothesized that the O1 antigen first appeared in RST19-1 and O2 in RST24-1 <em>E. coli</em> in humans. Then, O1 and O2-antigen horizontally transferred to human RST46-1, where a unique K1 capsule (K1-<em>cps</em>) first appeared. The Korean APEC and huExPEC share evolutionary CRISPR spacers but differ in molecular antibiograms and prophage contents. Thus, RST46-1 huExPEC transmitted and evolved in poultry. The zoonotic risks remain unknown, but the substantial virulence of the RST46-1 APEC indicates that the reverse zoonotic risk of huExPEC in poultry is alarming.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 3","pages":"Article 105462"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.micinf.2024.105468
Juliana Vaccari , Ana C. Borsanelli , Flávia R.F. Athayde , Júlia R. Saraiva , Thamiris N.M. Ramos , Iveraldo S. Dutra
As ruminants are frequently affected by periodontal diseases, understanding their microbial communities is crucial. In this pilot study, we analyzed subgingival biofilm samples of young cattle across different states: clinically healthy (n = 5), gingivitis (n = 5), and periodontitis (n = 5) using 16S rRNA gene sequencing and co-occurrence network analysis. The findings revealed that Proteobacteria was the predominant phylum across all conditions, with Fusobacteriota constituting 27.6 % of the microbiota in periodontitis-affected sites. In healthy sites, Moraxella (21.11 %), Neisseria (13.16 %), and Lautropia (7.69 %) were the predominant genera; in gingivitis-affected sites, the leading genera were Neisseria (23.65 %), Moraxella (18.95 %), and Conchiformibius (10.79 %); and in periodontitis sites, Caviibacter (19.78 %), Moraxella (16.13 %), and Fusobacterium (7.56 %) were most prevalent. Richness and dissimilarity analyses did not show significant differences across the clinical states, but differences were found between gingivitis and periodontitis sites (p = 0.01) in diversity. The co-occurrence networks highlighted significant variances in the central phyla across the phenotypes, with a higher number of positive interactions observed in periodontitis-affected sites. Consequently, this study demonstrated that the microbiota associated with periodontitis in young cattle exhibits greater diversity compared to gingivitis. Notably, in the deciduous dentition of cattle, the genera Caviibacter and Moraxella are pivotal in the context of periodontitis and periodontal health, respectively.
{"title":"Gingivitis- and periodontitis-associated microbiota in bovine deciduous incisor teeth – A preliminary study","authors":"Juliana Vaccari , Ana C. Borsanelli , Flávia R.F. Athayde , Júlia R. Saraiva , Thamiris N.M. Ramos , Iveraldo S. Dutra","doi":"10.1016/j.micinf.2024.105468","DOIUrl":"10.1016/j.micinf.2024.105468","url":null,"abstract":"<div><div>As ruminants are frequently affected by periodontal diseases, understanding their microbial communities is crucial. In this pilot study, we analyzed subgingival biofilm samples of young cattle across different states: clinically healthy (n = 5), gingivitis (n = 5), and periodontitis (n = 5) using 16S rRNA gene sequencing and co-occurrence network analysis. The findings revealed that Proteobacteria was the predominant phylum across all conditions, with Fusobacteriota constituting 27.6 % of the microbiota in periodontitis-affected sites. In healthy sites, <em>Moraxella</em> (21.11 %), <em>Neisseria</em> (13.16 %), and <em>Lautropia</em> (7.69 %) were the predominant genera; in gingivitis-affected sites, the leading genera were <em>Neisseria</em> (23.65 %), <em>Moraxella</em> (18.95 %), and <em>Conchiformibius</em> (10.79 %); and in periodontitis sites, <em>Caviibacter</em> (19.78 %), <em>Moraxella</em> (16.13 %), and <em>Fusobacterium</em> (7.56 %) were most prevalent. Richness and dissimilarity analyses did not show significant differences across the clinical states, but differences were found between gingivitis and periodontitis sites (p = 0.01) in diversity. The co-occurrence networks highlighted significant variances in the central phyla across the phenotypes, with a higher number of positive interactions observed in periodontitis-affected sites. Consequently, this study demonstrated that the microbiota associated with periodontitis in young cattle exhibits greater diversity compared to gingivitis. Notably, in the deciduous dentition of cattle, the genera <em>Caviibacter</em> and <em>Moraxella</em> are pivotal in the context of periodontitis and periodontal health, respectively.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 3","pages":"Article 105468"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The increase of antibiotic resistance calls for alternatives to control Helicobacter pylori, a Gram-negative bacterium associated with various gastric diseases. Bacteriophages (phages) can be highly effective in the treatment of pathogenic bacteria. Here, we developed a method to identify prophages in H. pylori genomes aiming at their future use in therapy. A polymerase chain reaction (PCR)-based technique tested five primer pairs on 74 clinical H. pylori strains. After the PCR screening, 14 strains most likely to carry prophages were fully sequenced. After that, a more holistic approach was taken by studying the complete genome of the strains. This study allowed us to identify 12 intact prophage sequences, which were then characterized concerning their morphology, virulence, and antibiotic-resistance genes. To understand the variability of prophages, a phylogenetic analysis using the sequences of all H. pylori phages reported to date was performed. Overall, we increased the efficiency of identifying complete prophages to 54.1 %. Genes with homology to potential virulence factors were identified in some new prophages. Phylogenetic analysis revealed a close relationship among H. pylori-phages, although there are phages with different geographical origins. This study provides a deeper understanding of H. pylori-phages, providing valuable insights into their potential use in therapy.
{"title":"Screening and in silico characterization of prophages in Helicobacter pylori clinical strains","authors":"Rute Ferreira , Graça Pinto , Eva Presa , Mónica Oleastro , Catarina Silva , Luís Vieira , Cláudia Sousa , Diana P. Pires , Ceu Figueiredo , Luís D.R. Melo","doi":"10.1016/j.micinf.2024.105429","DOIUrl":"10.1016/j.micinf.2024.105429","url":null,"abstract":"<div><div>The increase of antibiotic resistance calls for alternatives to control <em>Helicobacter pylori</em>, a Gram-negative bacterium associated with various gastric diseases. Bacteriophages (phages) can be highly effective in the treatment of pathogenic bacteria. Here, we developed a method to identify prophages in <em>H. pylori</em> genomes aiming at their future use in therapy. A polymerase chain reaction (PCR)-based technique tested five primer pairs on 74 clinical <em>H. pylori</em> strains. After the PCR screening, 14 strains most likely to carry prophages were fully sequenced. After that, a more holistic approach was taken by studying the complete genome of the strains. This study allowed us to identify 12 intact prophage sequences, which were then characterized concerning their morphology, virulence, and antibiotic-resistance genes. To understand the variability of prophages, a phylogenetic analysis using the sequences of all <em>H. pylori</em> phages reported to date was performed. Overall, we increased the efficiency of identifying complete prophages to 54.1 %. Genes with homology to potential virulence factors were identified in some new prophages. Phylogenetic analysis revealed a close relationship among <em>H. pylori</em>-phages, although there are phages with different geographical origins. This study provides a deeper understanding of <em>H. pylori</em>-phages, providing valuable insights into their potential use in therapy.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 3","pages":"Article 105429"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.micinf.2024.105467
Jônatas Santos Abrahão
Giant viruses have fascinated the scientific community due to their immense particles and extensive genomes. A significant surge of interest in the field has been observed over the past 20 years following the discovery of mimiviruses, the first amoeba-infecting viruses described. However, with the discovery of new amoeba viruses and those from other protists, the concept of "giant viruses" has become increasingly controversial in the scientific literature. This commentary revisits the historical and conceptual foundations of the term "giant virus" and explores its implications for virology.
{"title":"Revisiting the concept of giant viruses","authors":"Jônatas Santos Abrahão","doi":"10.1016/j.micinf.2024.105467","DOIUrl":"10.1016/j.micinf.2024.105467","url":null,"abstract":"<div><div>Giant viruses have fascinated the scientific community due to their immense particles and extensive genomes. A significant surge of interest in the field has been observed over the past 20 years following the discovery of mimiviruses, the first amoeba-infecting viruses described. However, with the discovery of new amoeba viruses and those from other protists, the concept of \"giant viruses\" has become increasingly controversial in the scientific literature. This commentary revisits the historical and conceptual foundations of the term \"giant virus\" and explores its implications for virology.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 3","pages":"Article 105467"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.micinf.2024.105437
Hang Liu , Mengyao Ma , Xinhao Jia , Mengwei Qian , Bo Pang , Muzi Li , Honglei Zhang , Shijie Ma , Lanlan Zheng
Transmissible gastroenteritis virus (TGEV) is a porcine intestinal pathogenic coronavirus that can cause acute intestinal diseases in pigs, especially in suckling piglets under two weeks of age, with a mortality rate of 100 %. Dendritic cells (DCs) are important antigen-presenting cells (APCs) that are essential for the initiation and modulation of immune responses in animals. In this study, we used monocyte-derived porcine DCs as an in vitro model of APCs to further study the pathogenic mechanism of TGEV. Our results demonstrated that TGEV successfully replicates in monocyte-derived porcine DCs, whereas UV-inactivated TGEV failed to infect these cells. Importantly, TGEV infection of DCs led to significant upregulation of swine leukocyte antigen II DR (SLA-DR), a key molecule in the major histocompatibility complex class II (MHC-II) family. We further demonstrated that the ORF3b nonstructural protein of TGEV significantly enhances SLA-DR expression at the transcriptional level in porcine DCs. This study provides new insights into the pathogenic mechanisms of TGEV.
传染性胃肠炎病毒（TGEV）是一种猪肠道致病性冠状病毒，可引起猪的急性肠道疾病，尤其是两周龄以下的哺乳仔猪，死亡率高达 100%。树突状细胞（DC）是重要的抗原递呈细胞（APC），对动物免疫反应的启动和调节至关重要。在本研究中，我们使用单核细胞衍生的猪 DCs 作为体外 APCs 模型，进一步研究 TGEV 的致病机制。我们的研究结果表明，TGEV 能在单核细胞衍生的猪 DCs 中成功复制，而紫外线灭活的 TGEV 却不能感染这些细胞。重要的是，TGEV 感染 DCs 会导致猪白细胞抗原 II DR（SLA-DR）显著上调，而猪白细胞抗原 II DR 是主要组织相容性复合体 II 类（MHC-II）家族中的一个关键分子。我们进一步证实，TGEV 的 ORF3b 非结构蛋白在转录水平上显著增强了猪 DCs 中 SLA-DR 的表达。这项研究为了解 TGEV 的致病机制提供了新的视角。
{"title":"TGEV nonstructural protein ORF3b upregulates the expression of SLA-DR at the transcriptional level in monocyte-derived porcine dendritic cells","authors":"Hang Liu , Mengyao Ma , Xinhao Jia , Mengwei Qian , Bo Pang , Muzi Li , Honglei Zhang , Shijie Ma , Lanlan Zheng","doi":"10.1016/j.micinf.2024.105437","DOIUrl":"10.1016/j.micinf.2024.105437","url":null,"abstract":"<div><div>Transmissible gastroenteritis virus (TGEV) is a porcine intestinal pathogenic coronavirus that can cause acute intestinal diseases in pigs, especially in suckling piglets under two weeks of age, with a mortality rate of 100 %. Dendritic cells (DCs) are important antigen-presenting cells (APCs) that are essential for the initiation and modulation of immune responses in animals. In this study, we used monocyte-derived porcine DCs as an in vitro model of APCs to further study the pathogenic mechanism of TGEV. Our results demonstrated that TGEV successfully replicates in monocyte-derived porcine DCs, whereas UV-inactivated TGEV failed to infect these cells. Importantly, TGEV infection of DCs led to significant upregulation of swine leukocyte antigen II DR (SLA-DR), a key molecule in the major histocompatibility complex class II (MHC-II) family. We further demonstrated that the ORF3b nonstructural protein of TGEV significantly enhances SLA-DR expression at the transcriptional level in porcine DCs. This study provides new insights into the pathogenic mechanisms of TGEV.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 3","pages":"Article 105437"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.micinf.2025.105469
Thais A. Amamura , Daniella dos S. Courrol , Angela S. Barbosa , Ildefonso A. Silva-Junior , Tiago F. da Silva , Leonardo M. Midon , Mario C. Cruz , Marcos B. Heinemann , Rosa M. Chura-Chambi , Ligia Morganti , Lourdes Isaac
Leptospirosis is a zoonosis caused by spirochete Leptospira. Pathogenic leptospires evade the Complement System, enabling their survival upon contact with normal human serum in vitro. In a previous study, we demonstrated that proteases secreted by pathogenic leptospires cleave several Complement proteins, including C3 and the opsonins C3b and iC3b. We hypothesize that these Leptospira proteases, such as thermolysin and leptolysin, may decrease the phagocytic activity of murine peritoneal macrophages. We observed decreased amounts of CR3 and CR4 using flow cytometry when these cells were treated with supernatant from the culture of pathogenic leptospires (SPL) for 24 h. Through confocal microscopy, we observed a reduction in TLR2, CD11b, and CD206 (mannose receptor) levels when these cells were treated with SPL or recombinant thermolysin for 24 h. Furthermore, opsonins such as C3b/iC3b deposited on the surface of pathogenic leptospires were clearly degraded in the presence of recombinant thermolysin or recombinant leptolysin. Consequently, when opsonized bacteria and macrophages were previously incubated with these proteases, phagocytic activity was diminished. These observations lead us to suggest that proteases secreted by pathogenic leptospires could degrade opsonins present in normal serum or deposited on the bacterial membrane, as well as cleave or inhibit macrophage surface molecules. Therefore, these proteases could interfere with the recognition and internalization by murine macrophages, favoring the spread of leptospires in the host.
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