Veterinary immunology and immunopathology最新文献_第2页

Waste milk consumption in Holstein calves: Effect on systemic adaptive immunity 荷斯坦犊牛废乳消耗：对全身适应性免疫的影响

IF 1.4 3区农林科学 Q4 IMMUNOLOGY

Veterinary immunology and immunopathology

Pub Date : 2026-01-01 DOI: 10.1016/j.vetimm.2025.111051

Karen Nascimento da Silva , Andrea Micke Moreno , Bianca Paola Santarosa , Larissa Miranda Padilha , Letícia Reis , Matheus Ricardo Curti Gonçalves , Marcelo Paulino das Neves , Viviani Gomes

Waste milk (WM) is unsuitable for human consumption due to the presence of drug residues, particularly antimicrobials and anti-inflammatory agent, as well as its high microbial load and somatic cell counts (SCC). Consequently, WM is commonly used to feed dairy calves. This study aimed to evaluate the effects of WM on humoral and cellular immunity in Holstein calves. Calves were assigned to three groups: saleable milk (SM, n = 10), pasteurized waste milk (PWM, n = 10), and raw WM (n = 10). Animals were monitored daily using standardized health scoring systems, and clinical samples were collected on days 7, 21, 35, 49, and 63 of life. Peripheral blood mononuclear cells (PBMC) were isolated, cultured, and stimulated with concanavalin A (ConA), Escherichia coli, Lactobacillus johnsonii, L. reuteri, and Bifidobacterium longum to assess proliferation (BrdU incorporation) and cytokine production (ELISA). Humoral responses were evaluated by serum total protein (STP), Brix refractometry, and IgG concentration. Generalized linear models revealed significant group differences. Clinical profiles were similar among groups. PWM and WM calves exhibited higher monocyte, lymphocyte, and total PBMC counts. Proliferation was greater in SM and PWM calves in response to ConA, E. coli, and L. johnsonii. SM and PWM calves showed higher IL-4 production, whereas WM calves had increased IL-17. IL-10 production was highest in SM. IgG concentrations increased across all groups; however, WM calves exhibited earlier and higher levels, while SM calves maintained the lowest. STP and Brix (%) trends paralleled IgG results. In conclusion, WM elicited an earlier and more intense pro-inflammatory immune response, PWM showed intermediate effects, and SM promoted greater IL-10 production, potentially modulating inflammation in calves.

由于存在药物残留，特别是抗菌剂和抗炎剂，以及其高微生物负荷和体细胞计数（SCC），废牛奶（WM）不适合人类食用。因此，WM通常用于喂养奶牛。本研究旨在评价WM对荷斯坦犊牛体液免疫和细胞免疫的影响。小牛被分为三组：可售奶（SM, n = 10），巴氏杀菌废奶（PWM, n = 10）和生奶（n = 10）。使用标准化健康评分系统对动物进行日常监测，并在生命的第7、21、35、49和63天收集临床样本。分离、培养外周血单核细胞（PBMC），并用豆豆蛋白A （ConA）、大肠杆菌、约氏乳杆菌、罗伊氏乳杆菌和长双歧杆菌刺激，评估其增殖（BrdU结合）和细胞因子产生（ELISA）。通过血清总蛋白（STP）、Brix折射法和IgG浓度来评估体液反应。广义线性模型显示了显著的组间差异。各组间临床情况相似。PWM和WM犊牛单核细胞、淋巴细胞和总PBMC计数较高。SM和PWM犊牛对ConA、E. coli和L. johnsonii的增殖反应更大。SM和PWM犊牛IL-4产量较高，而WM犊牛IL-17产量较高。SM中IL-10产量最高。各组IgG浓度均升高；而WM犊牛则表现得更早、更高，而SM犊牛则保持最低水平。STP和Brix（%）趋势与IgG结果一致。综上所述，WM引发了更早、更强烈的促炎免疫反应，PWM表现出中间效应，SM促进了IL-10的产生，可能调节了犊牛的炎症。

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引用次数: 0

Intradermal administration of a novel adjuvant cyclopolyphosphazene (CPZ-75B) in pigs induces innate immune responses comparable to poly[di(sodiumcarboxylatoethylphenoxy)phosphazene] (PCEP) 猪皮内注射一种新型佐剂环聚磷腈（CPZ-75B）可诱导与聚二羧酸钠乙基苯氧基磷腈（PCEP）相当的先天免疫反应。

IF 1.4 3区农林科学 Q4 IMMUNOLOGY

Veterinary immunology and immunopathology

Pub Date : 2026-01-01 DOI: 10.1016/j.vetimm.2025.111061

Dylan J. Chand , Rani Kanthan , Kezia R. Fourie , Leonie Bettin , Pooja Choudhary , Donaldson Magloire , Haoming Liu , Alison Jeffery , Barbara Ribeiro de Souza Cortez , Siew Hon Ng , Royford B. Magiri , Heather L. Wilson , George K. Mutwiri

In the present study, we evaluated innate immune responses induced by a novel cyclopolyphosphazene called CPZ-75B in piglets in the absence of antigen. Furthermore, we compared responses induced by this novel CPZ-75B adjuvant to PCEP, a known polyphosphazene adjuvant previously studied in a variety of animal species. Piglets were injected intradermally with 100 microliters of the following: PCEP (100 µg), CPZ-75B (133 µg) or PBS and the local cellular infiltrate and cytokine production were evaluated at the site of injection. CPZ-75B induced significant production of the cytokines IL-13, IL-1β, and IL-17A relative to the PBS control. However, CPZ-75B responses were significantly lower than those induced by PCEP. Both CPZ-75B and PCEP induced significant infiltration of injection sites with MHC II⁺ and CD3⁺ cells compared to PBS controls. In addition, PCEP but CPZ-75B induced significant increase in CD107a⁺ at the injection sites. Our study is the first to show that the new cyclophosphosphazene (CPZ-75B) induces transient innate immune responses at the injection site which may be important in stimulation of antigen-specific immunity if co-injected with vaccine antigens. Further studies are required to confirm the adjuvant activity of CPZ-75B when co-administered with antigens.

在本研究中，我们评估了一种名为CPZ-75B的新型环聚磷腈在缺乏抗原的情况下对仔猪的先天免疫反应。此外，我们比较了这种新型CPZ-75B佐剂对PCEP（一种已知的聚磷腈佐剂）的诱导反应，PCEP是一种已知的多磷腈佐剂，此前在多种动物中研究过。分别皮下注射100微升PCEP（100 µg）、CPZ-75B（133 µg）或PBS，观察注射部位局部细胞浸润和细胞因子产生情况。与PBS对照相比，CPZ-75B诱导细胞因子IL-13、IL-1β和IL-17A显著产生。但CPZ-75B的反应明显低于PCEP。与PBS对照相比，CPZ-75B和PCEP均能诱导MHC II+和CD3+细胞在注射部位的显著浸润。此外，除CPZ-75B外，PCEP诱导注射部位CD107a+显著升高。我们的研究首次表明，新的环磷腈（CPZ-75B）在注射部位诱导短暂的先天免疫反应，如果与疫苗抗原共同注射，这可能对刺激抗原特异性免疫很重要。需要进一步的研究来证实CPZ-75B与抗原共同施用时的佐剂活性。

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引用次数: 0

Transcriptomic profiling reveals early immune activation and metabolic remodeling in lymphoid tissues following in ovo Marek’s disease virus mRNA vaccination in chickens 转录组学分析揭示了蛋鸡马立克病病毒mRNA疫苗接种后淋巴组织的早期免疫激活和代谢重塑。

IF 1.4 3区农林科学 Q4 IMMUNOLOGY

Veterinary immunology and immunopathology

Pub Date : 2025-12-26 DOI: 10.1016/j.vetimm.2025.111052

Janan Shoja Doost , Alexander Yitbarek , Sarah K. Wootton , Shahriar Behboudi , Shayan Sharif

Marek’s disease virus (MDV) is a highly contagious oncogenic alphaherpesvirus that continues to threaten global poultry production, highlighting the need for next-generation vaccines. Although in ovo delivery of conventional MDV vaccines has been effective, vaccine leakiness has accelerated viral evolution by promoting the selection of more virulent, immune-evasive strains. mRNA vaccines offer a flexible and rapidly adaptable platform capable of inducing potent immune responses, yet their application against MDV remains unexplored in the in ovo context. Here, we report the first in ovo administration of a bivalent MDV mRNA vaccine encoding glycoprotein B (gB) and phosphoprotein 38 (pp38). RNA sequencing of the spleen and bursa of Fabricius at 12-, 24-, and 48-hours post-vaccination revealed distinct, time- and tissue-specific transcriptional programs. In the spleen, differential expression analysis (fold-change ≥ 2, padj < 0.05) demonstrated early activation of caudal-type homeobox 1 (CDX1) and signal transducer and activator of transcription 1 (STAT1), together with interferon-stimulated antiviral genes MX dynamin-like GTPase 1 (MX1), 2′–5′-oligoadenylate synthetase-like (OASL), and interferon-induced protein with tetratricopeptide repeats 5 (IFIT5). In contrast, the bursa exhibited persistent modulation of colipase (CLPS), chymotrypsinogen B1 (CTRB1), and deoxyribonuclease I (DNASE1), indicating metabolic and apoptotic remodeling. These results demonstrate that in ovo mRNA vaccination against MDV rapidly activates organ-specific immune and metabolic pathways, providing a transcriptomic framework for the rational design of poultry mRNA vaccines.

马立克病病毒（Marek's disease virus， MDV）是一种高度传染性的致癌甲型疱疹病毒，它继续威胁着全球家禽生产，这凸显了对下一代疫苗的需求。尽管常规MDV疫苗在蛋内递送是有效的，但疫苗泄漏通过促进选择毒性更强、免疫逃避的毒株，加速了病毒的进化。mRNA疫苗提供了一个灵活和快速适应的平台，能够诱导有效的免疫反应，但它们在禽类环境中针对MDV的应用仍未探索。在这里，我们首次报道了一种编码糖蛋白B （gB）和磷酸化蛋白38 （pp38）的二价MDV mRNA疫苗的蛋注射。在接种疫苗后12、24和48小时对脾脏和法氏囊进行RNA测序，揭示了不同的、时间和组织特异性的转录程序。在脾脏中，差异表达分析（fold-change≥2,padj < 0.05）显示尾型同源盒1 （CDX1）和转录信号换能器和激活因子1 （STAT1）的早期激活，以及干扰素刺激的抗病毒基因MX动力蛋白样GTPase 1 (MX1), 2'-5'-寡腺苷酸合成酶样（OASL）和干扰素诱导的四肽重复蛋白5 （IFIT5）。相比之下，法氏囊表现出持续的胶原酶（CLPS）、胰凝乳蛋白酶原B1 （CTRB1）和脱氧核糖核酸酶I （DNASE1）的调节，表明代谢和凋亡重构。这些结果表明，针对MDV的鸟蛋mRNA疫苗可快速激活器官特异性免疫和代谢途径，为合理设计家禽mRNA疫苗提供了转录组学框架。

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引用次数: 0

The impact of subclinical hyperketonemia on primary immunoglobulins, immune-antioxidant enzymes and acute-phase proteins in postparturient Indian mithun (Bos frontalis) cows reared semi-intensively 亚临床高酮血症对半密集饲养的产后印度米顿牛初级免疫球蛋白、免疫抗氧化酶和急性期蛋白的影响

IF 1.4 3区农林科学 Q4 IMMUNOLOGY

Veterinary immunology and immunopathology

Pub Date : 2025-12-19 DOI: 10.1016/j.vetimm.2025.111050

Vivek Joshi , Lipenthung Y. Ezung , J.K. Chamuah , R. Vikram , Kezhavitou Vupru , Kobu Khate , M.H. Khan , P.S. Girish

Managing subclinical ketosis (SCK), which Indian mithun (Bos frontalis) cows experience at least once within four weeks postpartum, requires understanding the interaction of immuno-inflammatory mediators and hyperketonemia. This study aimed to explore the interplay of SCK with the major immunoglobulins (IgG, IgA), acute-phase proteins (haptoglobin, Hpt; serum amyloid A, SAA), and immune-antioxidant enzymes (lactoperoxidase, LPO; lysozyme, LZM; superoxide dismutase, SOD) in postparturient mithun cows. Thirty SCK mithun cows were selected based on blood BHBA (≥1.10 mmol/l) from two semi-intensive mithun farms. Serum concentrations of IgG, IgA, Hpt, SAA, LPO, LZM and SOD were measured at 1, 2 and 4 weeks postpartum by enzyme-linked immunosorbent assay. SCK group had significantly lower IgA values in the first week postpartum and higher IgG values in the second and fourth week. Higher concentrations (P < 0.05) of Hpt, SAA, SOD, and LZM were seen in SCK mithuns during the first week postpartum compared to healthy controls. No significant differences were observed in postpartal LPO. Hpt and SAA concentrations showed a significant positive correlation with BHBA (R=0.39, P < 0.001 and R=0.27, P < 0.001, respectively) and NEFA (R=0.17, P < 0.01 and R=0.13, P < 0.001, respectively). Serum IgA and SCK biomarkers (BHBA, NEFA) had negative relationships (R=0.44, P < 0.001 and R=0.41, P < 0.05, respectively). These findings illustrate that immunologic dysregulation, inflammation and oxidative stress mediate less severe ketosis (SCK) in the early postpartum mithun cows. Conclusively, this justifies the need of developing strategies to control postpartum hyperketonemia in mithun cows. Future studies on the viability of using antiinflammatory and antioxidant therapy to prevent SCK from worsening to clinical ketosis are warranted.

印度mithun （Bos frontalis）奶牛在产后四周内至少经历一次亚临床酮症（SCK），需要了解免疫炎症介质和高酮血症的相互作用。本研究旨在探讨SCK与产后乳牛主要免疫球蛋白（IgG、IgA）、急性期蛋白（haptoglobin、Hpt、血清淀粉样蛋白A、SAA）和免疫抗氧化酶（乳酸过氧化物酶、LPO、溶菌酶、超氧化物歧化酶、SOD）的相互作用。以血BHBA（≥1.10 mmol/l）为指标，从2个半集约化密乳农场选择30头SCK密乳奶牛。采用酶联免疫吸附法测定产后1、2、4周血清IgG、IgA、Hpt、SAA、LPO、LZM、SOD的浓度。SCK组产后1周IgA值明显降低，产后2、4周IgG值明显升高。与健康对照组相比，产后第一周SCK组Hpt、SAA、SOD和LZM浓度较高（P <； 0.05）。产后LPO无显著性差异。Hpt和SAA浓度与BHBA （R=0.39, P <； 0.001和R=0.27, P <； 0.001）和NEFA （R=0.17, P <； 0.01和R=0.13, P <； 0.001）呈显著正相关。血清IgA与SCK生物标志物（BHBA、NEFA）呈负相关（R=0.44, P <； 0.001，R=0.41, P <； 0.05）。这些发现表明，免疫失调、炎症和氧化应激介导产后早期母牛较轻的酮症（SCK）。最后，这证明需要制定策略来控制产后高酮血症的母牛。未来研究使用抗炎和抗氧化治疗防止SCK恶化为临床酮症的可行性是有必要的。

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引用次数: 0

Evaluation of the effect of exogenous 25-(OH)D3 vitamin administration on colostral and serum cytokine levels, lactoferrin and IgG concentration in prepartum period holstein heifer 外源性25-(OH)D3维生素对孕前期荷斯坦母牛初乳和血清细胞因子水平、乳铁蛋白和IgG浓度的影响

IF 1.4 3区农林科学 Q4 IMMUNOLOGY

Veterinary immunology and immunopathology

Pub Date : 2025-12-18 DOI: 10.1016/j.vetimm.2025.111049

Murat Uzti̇mür

The aim of this study was to evaluate the effects of a single dose of 25-(OH)D3 vitamin injection in pregnant holstein heifers on cytokine concentrations (IL-6 and IFN-γ) in heifer colostrum and serum, colostral lactoferrin, and IgG and vitamin D concentrations in calves. The control group (n: 10) and the vitamin D group (n: 10) were composed of heifer Holstein 8 ± 2 days before calving. Blood samples were collected on day 265 ± 2 of gestation in the vitamin D and control groups, before vitamin D and physiological saline administration, and at the time of parturition. Colostrum and serum samples were analyzed for lactoferrin, IgG, IL-6, and IFN-γ by bovine-specific ELISA, solid-matter digital refractometry, and vitamin D by LC-MS/MS. The colostral IFN-γ (p < 0.015), IgG (p < 0.035), lactoferrin (p < 0.001), and Brix (p < 0.035) concentrations of the vitamin D group were significantly higher than those of the control group. Serum IL-6 (p<0.002) and IF-γ (p<0.001) concentrations were significantly lower in the group that received vitamin D at parturition compared to the control group. In contrast, serum 25-(OH)D concentrations in heifers treated with vitamin D were significantly higher than in the control group (p<0.003). The serum 25-(OH)D concentration of calves born from heifers administered vitamin D was significantly higher than the control group (p < 0.006). Serum vitamin D concentration in calving cows showed a negative correlation with IL-6 (r=-0.663, p<0.001) and IFN-γ (r=-0.687, p<0.001) levels, while it showed a positive correlation with colostrum IFN-γ (r=0.446, p<0.048), colostral lactoferrin (r=0.686, p<0.001), and calf serum vitamin D concentration (r=0.598, p<0.005). In conclusion, this study determined that administering vitamin D to holstein heifer increased colostrum cytokine concentrations and lactoferrin levels, decreased serum pro-inflammatory cytokine concentrations at parturition, and increased colostrum IgG and Brix values. Additionally, the increased serum vitamin D concentration had a positive impact on the health and well-being of the animals by suppressing inflammatory cytokines. Vitamin D supplementation in holstein heifers can increase vitamin D levels in calves and significantly improve colostrum quality and cow health.

本研究旨在评价妊娠荷斯坦母牛单剂量25-(OH)D3维生素注射对犊牛初乳和血清中细胞因子（IL-6和IFN-γ）、初乳乳铁蛋白、IgG和维生素D浓度的影响。对照组（n: 10）和维生素D组（n: 10）选用产犊前2 D的荷斯坦8号奶牛 ± 。维生素D组和对照组分别于妊娠第265天 ± 2、服用维生素D和生理盐水前和分娩时采集血样。采用牛特异性ELISA、固体物质数字折射法和LC-MS/MS分析牛初乳和血清样品中的乳铁蛋白、IgG、IL-6和IFN-γ。维生素D组初乳IFN-γ （p <； 0.015）、IgG （p <； 0.035）、乳铁蛋白（p <； 0.001）和Brix （p <； 0.035）浓度显著高于对照组。与对照组相比，分娩时服用维生素D组血清IL-6（0.002）和IF-γ(0.001)浓度显著降低。相比之下，维生素D处理的犊牛血清25-(OH)D浓度显著高于对照组（p < 0.05;0.003）。添加维生素D的母牛所生犊牛血清25-(OH)D浓度显著高于对照组（p <； 0.006）。犊牛血清维生素D浓度与IL-6 （r=-0.663, p<0.001）和IFN-γ (r=-0.687, p<0.001)水平呈负相关，与初乳IFN-γ (r=0.446, p<0.048)、初乳乳铁蛋白（r=0.686, p<0.001）和犊牛血清维生素D浓度（r=0.598, p<0.005）呈正相关。综上所述，本研究确定，给予荷斯坦母牛维生素D可提高初乳细胞因子浓度和乳铁蛋白水平，降低分娩时血清促炎细胞因子浓度，提高初乳IgG和Brix值。此外，血清维生素D浓度的增加通过抑制炎症细胞因子对动物的健康和福祉产生积极影响。在荷斯坦母牛饲粮中添加维生素D可提高犊牛体内维生素D水平，显著改善初乳品质和奶牛健康状况。

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引用次数: 0

Quantification of intrinsic MDR-1 gene expression in different immunophenotypes of canine multicentric lymphomas 犬多中心淋巴瘤不同免疫表型内生性耐多药-1基因表达的定量分析。

IF 1.4 3区农林科学 Q4 IMMUNOLOGY

Veterinary immunology and immunopathology

Pub Date : 2025-12-12 DOI: 10.1016/j.vetimm.2025.111048

Rosina Sánchez-Solé , Florencia Mosquillo , Nariné Balemian , Paula Pessina , Martín Breijo

Little is known about the intrinsic expression of the multidrug resistance gene type 1 (MDR-1) in dogs with multicentric lymphoma of different immunophenotypes assessed by qRT-PCR. The purpose of this study is to evaluate the level of MDR-1 expression by real-time PCR on biopsy samples from enlarged lymph nodes of 29 untreated dogs with different immunophenotypes of multicentric lymphoma (B-cell vs CD45+ T-cell vs CD45− T-cell). Cell lineage was established by flow cytometry based on the expression of CD3, CD4, CD5, CD8, CD21, and CD45. Our results indicate that MDR-1 gene expression is detectable in nearly 80 % of newly diagnosed canine lymphomas of different immunophenotypes. MDR-1 expression was undetectable in 5/13 of B-cell lymphomas and 1/10 of CD45+ T-cell lymphomas, while all CD45- T-cell lymphomas were quantifiable. By analyzing the level of MDR-1 gene expression in quantifiable samples, the expression of MDR-1 in dogs with CD45- T-cell lymphoma was higher than observed in B and CD45+ T-cell lymphomas, suggesting that the lymphoma immunophenotype is an important factor that influences the expression levels of the MDR-1 gene.

qRT-PCR检测不同免疫表型的多中心淋巴瘤犬体内多药耐药基因1型（MDR-1）的内在表达情况尚不清楚。本研究的目的是通过实时荧光定量PCR （real-time PCR）评估29只不同免疫表型（b细胞、CD45+ t细胞、CD45- t细胞）的多中心淋巴瘤狗肿大淋巴结活检样本中MDR-1的表达水平。通过流式细胞术检测CD3、CD4、CD5、CD8、CD21和CD45的表达，建立细胞谱系。我们的研究结果表明，在近80% %的不同免疫表型的新诊断犬淋巴瘤中可检测到MDR-1基因表达。5/13的b细胞淋巴瘤和1/10的CD45+ t细胞淋巴瘤中检测不到MDR-1的表达，而所有CD45- t细胞淋巴瘤均可量化。通过对可量化样本中MDR-1基因表达水平的分析，CD45- t细胞淋巴瘤犬中MDR-1的表达高于B型和CD45+ t细胞淋巴瘤，提示淋巴瘤免疫表型是影响MDR-1基因表达水平的重要因素。

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引用次数: 0

Transcriptomic signatures of cytomorphological heterogeneity in canine transmissible venereal tumor 犬传染性性病肿瘤细胞形态学异质性的转录组学特征。

IF 1.4 3区农林科学 Q4 IMMUNOLOGY

Veterinary immunology and immunopathology

Pub Date : 2025-12-11 DOI: 10.1016/j.vetimm.2025.111044

Fabián D. López-Valbuena , William F. Osorio-Zambrano , Luis M. Montoya-Flórez , Noeme Sousa-Rocha

Background

Canine transmissible venereal tumor (CTVT) is a naturally occurring, clonally transmissible cancer that persists in hosts through mechanisms of immune evasion and adaptation. It presents three cytomorphological subtypes—plasmacytoid, lymphocytoid, and mixed—each linked to distinct clinical behaviors and therapeutic responses. These phenotypes likely reflect divergent transcriptional programs, but their molecular basis remains poorly defined.

Objective

This study aimed to describe transcriptional profiles associated with CTVT subtypes and identify pathways underlying their biological behaviors.

Methods

We analyzed RNA-Seq data from 10 CTVT tumors classified into plasmacytoid, lymphocytoid, and mixed subtypes. Differential expression analysis was conducted using DESeq2, followed by functional enrichment (DAVID), protein–protein interaction analysis (STRING), and co-expression network construction with Pearson correlation and Louvain clustering.

Results

The strongest transcriptional divergence was observed between plasmacytoid and lymphocytoid subtypes, with 237 differentially expressed genes enriched in immune pathways. Plasmacytoid tumors showed upregulation of immune-related genes, including CXCL10, IL15, CD74, and DLA-DQA1, forming MHC-II co-expression modules. Lymphocytoid tumors upregulated genes involved in DNA repair and proliferation, such as ATM, PCBP1, and CDK1. Comparisons with the mixed subtype revealed fewer DEGs and limited enrichment, suggesting an intermediate transcriptional profile.

Conclusions

Our findings reveal subtype-specific transcriptional programs in CTVT. The plasmacytoid subtype displayed enriched immune signatures, particularly in antigen presentation and cytokine signaling, while the lymphocytoid subtype showed a proliferative, immune-silent profile. Mixed tumors exhibited intermediate or transitional features. These insights support a molecular taxonomy of CTVT and highlight potential biomarkers for future prognostic and therapeutic stratification.

背景：犬传染性性病肿瘤（CTVT）是一种自然发生的，通过免疫逃避和适应机制在宿主体内持续存在的克隆传染性癌症。它呈现出三种细胞形态亚型-浆细胞样，淋巴细胞样和混合-每一种都与不同的临床行为和治疗反应有关。这些表型可能反映了不同的转录程序，但它们的分子基础仍然不明确。目的：本研究旨在描述与CTVT亚型相关的转录谱，并确定其生物学行为背后的途径。方法：我们分析了10例CTVT肿瘤的RNA-Seq数据，这些肿瘤分为浆细胞样、淋巴细胞样和混合亚型。采用DESeq2进行差异表达分析，随后进行功能富集分析（DAVID）、蛋白互作分析（STRING），并利用Pearson相关和Louvain聚类构建共表达网络。结果：浆细胞样亚型和淋巴细胞样亚型之间的转录差异最大，237个差异表达基因在免疫途径中富集。浆细胞样肿瘤表达免疫相关基因上调，包括CXCL10、IL15、CD74和DLA-DQA1，形成MHC-II共表达模块。淋巴细胞样肿瘤上调参与DNA修复和增殖的基因，如ATM、PCBP1和CDK1。与混合亚型的比较显示，deg较少，富集程度有限，表明其转录谱介于中间。结论：我们的研究结果揭示了CTVT的亚型特异性转录程序。浆细胞样亚型表现出丰富的免疫特征，特别是在抗原呈递和细胞因子信号传导方面，而淋巴细胞样亚型表现出增殖性、免疫沉默性。混合性肿瘤表现为中间或过渡性特征。这些见解支持CTVT的分子分类学，并强调了未来预后和治疗分层的潜在生物标志物。

{"title":"Transcriptomic signatures of cytomorphological heterogeneity in canine transmissible venereal tumor","authors":"Fabián D. López-Valbuena , William F. Osorio-Zambrano , Luis M. Montoya-Flórez , Noeme Sousa-Rocha","doi":"10.1016/j.vetimm.2025.111044","DOIUrl":"10.1016/j.vetimm.2025.111044","url":null,"abstract":"<div><h3>Background</h3><div>Canine transmissible venereal tumor (CTVT) is a naturally occurring, clonally transmissible cancer that persists in hosts through mechanisms of immune evasion and adaptation. It presents three cytomorphological subtypes—plasmacytoid, lymphocytoid, and mixed—each linked to distinct clinical behaviors and therapeutic responses. These phenotypes likely reflect divergent transcriptional programs, but their molecular basis remains poorly defined.</div></div><div><h3>Objective</h3><div>This study aimed to describe transcriptional profiles associated with CTVT subtypes and identify pathways underlying their biological behaviors.</div></div><div><h3>Methods</h3><div>We analyzed RNA-Seq data from 10 CTVT tumors classified into plasmacytoid, lymphocytoid, and mixed subtypes. Differential expression analysis was conducted using DESeq2, followed by functional enrichment (DAVID), protein–protein interaction analysis (STRING), and co-expression network construction with Pearson correlation and Louvain clustering.</div></div><div><h3>Results</h3><div>The strongest transcriptional divergence was observed between plasmacytoid and lymphocytoid subtypes, with 237 differentially expressed genes enriched in immune pathways. Plasmacytoid tumors showed upregulation of immune-related genes, including <em>CXCL10</em>, <em>IL15</em>, <em>CD74</em>, and <em>DLA-DQA1</em>, forming MHC-II co-expression modules. Lymphocytoid tumors upregulated genes involved in DNA repair and proliferation, such as <em>ATM</em>, <em>PCBP1</em>, and <em>CDK1</em>. Comparisons with the mixed subtype revealed fewer DEGs and limited enrichment, suggesting an intermediate transcriptional profile.</div></div><div><h3>Conclusions</h3><div>Our findings reveal subtype-specific transcriptional programs in CTVT. The plasmacytoid subtype displayed enriched immune signatures, particularly in antigen presentation and cytokine signaling, while the lymphocytoid subtype showed a proliferative, immune-silent profile. Mixed tumors exhibited intermediate or transitional features. These insights support a molecular taxonomy of CTVT and highlight potential biomarkers for future prognostic and therapeutic stratification.</div></div>","PeriodicalId":23511,"journal":{"name":"Veterinary immunology and immunopathology","volume":"292 ","pages":"Article 111044"},"PeriodicalIF":1.4,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145820988","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}

引用次数: 0

BoAHV-1 and −5 differentially modulate TLR3 signaling and type I IFN in neural cells BoAHV-1和- 5在神经细胞中差异调节TLR3信号和I型IFN

IF 1.4 3区农林科学 Q4 IMMUNOLOGY

Veterinary immunology and immunopathology

Pub Date : 2025-12-11 DOI: 10.1016/j.vetimm.2025.111046

Juan José Rosales , María Belén Brunner , Milagros Junco , Lucía Martínez Cuesta , Maia Marin , Sandra Pérez

Varicellovirus bovinealpha (BoAHV)-1 and −5 (formerly known as bovine alphaherpesviruses 1 and 5) are closely-related neurotropic viruses with distinct neuropathogenic potential. In this study, we investigated how BoAHV-1 and BoAHV-5 modulate toll-like receptor 3 (TLR3) signaling pathway and type I interferon (IFN) response in neural cells. Stimulation of neural cells with the TLR3 agonist polyinosinic:polycytidylic acid (poly I:C) induced transient upregulation of TRIF, IRF-3, NF-κB, and IFN-α, mainly at early time points. BoAHV-1 infection triggered a delayed but sustained upregulation of IRF-3 and IFN-β, coinciding with a progressive increase in TRIF expression, which was subsequently downregulated at later stages. In contrast, BoAHV-5 infection elicited a rapid and robust early innate immune response characterized by strong IRF-3, NF-κB, and IFN-α transcription. Furthermore, BoAHV-5 induced sustained high IFN-β levels throughout infection, suggesting engagement of alternative antiviral pathways, likely RIG-I/MDA-5 receptors. These findings highlight distinct immunomodulatory strategies employed by BoAHV-1 and BoAHV-5 in neural cells. While BoAHV-1 infection is characterized by a delayed antiviral response, BoAHV-5 mounts a strong but transient immune response. BoAHV-5 suppresses TLR3 signaling and likely activates alternative pathways, such as RIG-I/MDA5 signaling. Overall, this study provides additional insight on BoAHV manipulation of the innate immunity and its role in neuropathogenesis.

牛α水痘病毒(BoAHV)-1和- 5（以前称为牛α疱疹病毒1和5）是密切相关的嗜神经病毒，具有明显的神经致病性。在本研究中，我们研究了BoAHV-1和BoAHV-5如何调节神经细胞中toll样受体3 （TLR3）信号通路和I型干扰素（IFN）反应。TLR3激动剂多肌苷：多胞苷酸（poly I:C）刺激神经细胞可诱导TRIF、IRF-3、NF-κB和IFN-α的短暂上调，且主要发生在早期时间点。BoAHV-1感染引发IRF-3和IFN-β的延迟但持续的上调，与TRIF表达的进行性增加相一致，随后在后期下调。相比之下，BoAHV-5感染引发了快速而强大的早期先天免疫反应，其特征是强烈的IRF-3、NF-κB和IFN-α转录。此外，BoAHV-5在整个感染过程中诱导持续高水平的IFN-β，表明参与了其他抗病毒途径，如rig - 1 /MDA-5受体。这些发现突出了BoAHV-1和BoAHV-5在神经细胞中采用的不同免疫调节策略。BoAHV-1感染的特点是抗病毒反应延迟，而BoAHV-5则产生强烈但短暂的免疫反应。BoAHV-5抑制TLR3信号，并可能激活其他途径，如RIG-I/MDA5信号。总的来说，这项研究为BoAHV操纵先天免疫及其在神经发病机制中的作用提供了额外的见解。

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引用次数: 0

G-CSF in feline medicine: From molecular mechanisms to clinical applications G-CSF在猫科药物中的应用：从分子机制到临床应用。

IF 1.4 3区农林科学 Q4 IMMUNOLOGY

Veterinary immunology and immunopathology

Pub Date : 2025-12-07 DOI: 10.1016/j.vetimm.2025.111045

Lei Xiong , Zhang Zhang , Xin Liu , Qiang Lai , Fei Zheng , Xiaozhen Peng , Weifang Luo , Yi Wang

Background

Granulocyte colony-stimulating factor (G-CSF) is a crucial hematopoietic growth factor essential for granulopoiesis, inflammation, and immune responses in humans and animals. Although widely used in human medicine for neutropenia and transplantation support, its applications in feline medicine, encompassing neutropenia, infection management, and transplantation, remain underexplored, with limited comprehensive reviews. A significant limitation of recombinant human G-CSF (rhG-CSF) treatment in cats is the risk of developing neutralizing antibodies, which can target G-CSF and potentially reduce its efficacy. Developing feline-specific or long-acting variants offers potential solutions.

Methods

A comprehensive literature search was performed using PubMed and other databases up to August 1, 2025. Search terms included “G-CSF”, “granulocyte colony-stimulating factor”, “feline”, and “cat”. Studies reporting the clinical use of G-CSF in cats were included.

Results

rhG-CSF administration elevated neutrophil and lymphocyte counts but could induce transient neutropenia and immunogenicity. In contrast, recombinant feline G-CSF (rfG-CSF) demonstrated improved bioactivity and did not generate anti-drug antibodies in small-scale studies with follow-up periods extending beyond one year. Novel long-acting variants, including PEGylated rfG-CSF (PEG-rfG-CSF) and a fusion protein, exhibited prolonged half-life and enhanced efficacy compared to standard forms.

Conclusion

rfG-CSF represents a promising therapeutic alternative to rhG-CSF for managing neutropenia in cats, primarily due to its lack of immunogenicity. Future development efforts should focus on optimizing these long-acting formulations and maximizing bioactivity to facilitate widespread clinical adoption and commercialization in veterinary medicine.

背景：粒细胞集落刺激因子（G-CSF）是一种重要的造血生长因子，对人类和动物的粒细胞生成、炎症和免疫反应至关重要。尽管在人类医学中广泛用于中性粒细胞减少和移植支持，但其在猫医学中的应用，包括中性粒细胞减少、感染管理和移植，仍未得到充分探索，综合评价有限。重组人G-CSF （rhG-CSF）治疗猫的一个显着局限性是产生中和抗体的风险，这些抗体可以靶向G-CSF并可能降低其疗效。开发针对猫科动物的或长效的变种提供了潜在的解决方案。方法：综合检索PubMed等数据库，检索时间截止到2025年8月1日。搜索词包括“G-CSF”、“粒细胞集落刺激因子”、“猫科动物”和“猫”。研究报告了G-CSF在猫中的临床应用。结果：rhG-CSF使中性粒细胞和淋巴细胞计数升高，但可引起短暂性中性粒细胞减少和免疫原性。相比之下，在随访超过一年的小规模研究中，重组猫G-CSF （rfG-CSF）显示出更好的生物活性，并且没有产生抗药物抗体。新的长效变体，包括聚乙二醇化的rfG-CSF （PEG-rfG-CSF）和融合蛋白，与标准形式相比，表现出更长的半衰期和更强的功效。结论：rfG-CSF是治疗猫中性粒细胞减少症的有希望的替代rhG-CSF的治疗方案，主要是由于其缺乏免疫原性。未来的开发工作应侧重于优化这些长效制剂和最大化生物活性，以促进兽药的广泛临床应用和商业化。

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引用次数: 0

Functional resilience of Kangayam cattle under thermal stress: Insights into cellular and immune adaptations 热应激条件下康亚姆牛的功能恢复力：细胞和免疫适应的见解

IF 1.4 3区农林科学 Q4 IMMUNOLOGY

Veterinary immunology and immunopathology

Pub Date : 2025-12-07 DOI: 10.1016/j.vetimm.2025.111047

Kandasamy Rajamanickam , Sarika Sahu , Manoharan Azhaguraja , Visha Pasuvalingam , Periyasamy Vijayakumar , Arumugam Sakthivel Selvan , Elango Ayyasamy

The study for the first time, investigates cellular and immune resilience of Kangayam cattle to heat stress in comparison with Jersey cattle. The study involves twenty-four adult cows (Kangayam cows (n = 12); Jersey cows (n = 12)) allocated randomly into four different groups of six animals each (Kangayam heat stress, Kangayam control, Jersey heat stress, Jersey control). The study period (45-days) spans over April to May months of the summer season during which the animals in control group were housed in a shed, while the other groups were expose to environmental thermal stress daily. At the end of experimental period, haematology, biochemical, cortisol, heat shock protein 70 and cytokines levels, redox status and peripheral blood mononuclear cell responses were recorded. Results revealed reduced variability in haemato-biochemical parameters, cortisol, NEFA and haptoglobin levels and significantly elevated (P < 0.001) heat shock protein 70 in heat stressed Kangayam cattle. Moreover, Kangayam cattle exhibited high stability in the expression of IL-1β, IL-6 and tumor necrosis factor and also their redox status like antioxidant enzymes activities, malondialdehyde and intracellular ROS levels, free radical scavenging activity and total thiol level were unaltered during thermal stress. In addition, Kangayam cattle PBMCs demonstrated unaltered apoptotic rate with preserved DNA integrity and increased mitochondrial membrane potential and decreased matrix metalloproteinase 2 and 9 activities. In conclusion, the current study highlights the superior cellular and immune resilience of Kangayam cattle under thermal stress conditions for the first of its kind.

本研究首次以泽西牛为对照，研究了康加雅牛对热应激的细胞和免疫恢复能力。研究对象为24头成年奶牛(Kangayam奶牛（n = 12）；将泽西奶牛（n = 12）随机分为4组，每组6头（Kangayam热应激组、Kangayam对照组、Jersey热应激组、Jersey对照组）。试验期（45 d）为夏季4 ~ 5月，对照组在棚内饲养，其余各组每天进行环境热应激。实验结束时，记录大鼠血液学、生化、皮质醇、热休克蛋白70和细胞因子水平、氧化还原状态和外周血单个核细胞反应。结果显示，热应激的康亚姆牛血液生化参数、皮质醇、NEFA和接触球蛋白水平的变异性降低，热休克蛋白70显著升高（P <； 0.001）。此外，在热应激条件下，康阳牛IL-1β、IL-6和肿瘤坏死因子的表达具有较高的稳定性，抗氧化酶活性、丙二醛和细胞内ROS水平、自由基清除活性和总硫醇水平等氧化还原状态未发生变化。此外，康亚姆牛pbmc细胞凋亡率保持不变，DNA完整性保持不变，线粒体膜电位升高，基质金属蛋白酶2和9活性降低。综上所述，本研究首次突出了康加yam牛在热应激条件下优越的细胞和免疫恢复能力。

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引用次数: 0