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Sorafenib inhibits myeloid-derived suppressor cell infiltration in canine transitional cell carcinoma 索拉非尼抑制犬移行细胞癌骨髓源性抑制细胞浸润
IF 1.4 3区 农林科学 Q4 IMMUNOLOGY Pub Date : 2025-10-26 DOI: 10.1016/j.vetimm.2025.111019
Shohei Yokota , Wataru Fujii , Tomoki Motegi , Mao Komori , Reo Nishi , James K. Chambers , Kazuyuki Uchida , Tomohiro Yonezawa , Yasuyuki Momoi , Shingo Maeda
Myeloid-derived suppressor cells (MDSCs)—immature cells with immunosuppressive properties—are promising therapeutic targets for cancer immunotherapy. However, established therapies targeting MDSCs remain lacking, and novel molecules are needed to regulate MDSCs. Sorafenib, a tyrosine kinase (TRK) inhibitor, suppresses MDSCs. As TRKs regulate chemokine production, we hypothesized that sorafenib inhibits MDSCs by regulating chemokine production. This study aimed to investigate the effect of sorafenib on MDSCs and its underlying mechanism in canine transitional cell carcinoma (cTCC). Sorafenib reduced the number of MDSCs and downregulated CX3CL1 expression in the tumor tissues of cTCC-transplanted mice. Vascular endothelial growth factor A (VEGF-A) and platelet derived growth factor-BB (PDGF-BB) recombinant protein, the target axis of sorafenib, increased CX3CL1 expression in cTCC cell line. Furthermore, a positive correlation was observed between urinary levels of CX3CL1 and VEGF-A in cTCC cases. These results indicated that VEGF-A signaling can regulate CX3CL1 expression. Next, we analyzed whether CX3CL1 accelerates MDSC infiltration. MDSCs expressed CX3CR1, the receptor for CX3CL1, and migrated toward recombinant CX3CL1 protein in a dose-dependent manner. In a cTCC-transplanted mouse model, CX3CL1 depletion or treatment with a CX3CR1 inhibitor showed anti-tumor effects and reduced MDSCs in the tumor tissue. Overall, our results indicated that CX3CL1 promotes MDSC infiltration, and the CX3CL1/CX3CR1 axis could be a therapeutic target for regulating MDSCs in dogs with cTCC.
髓源性抑制细胞(MDSCs)是一种具有免疫抑制特性的未成熟细胞,是癌症免疫治疗中很有希望的治疗靶点。然而,针对MDSCs的既定治疗方法仍然缺乏,需要新的分子来调节MDSCs。索拉非尼是一种酪氨酸激酶(TRK)抑制剂,可抑制MDSCs。由于TRKs调节趋化因子的产生,我们假设索拉非尼通过调节趋化因子的产生来抑制MDSCs。本研究旨在探讨索拉非尼对犬移行细胞癌(cTCC) MDSCs的影响及其潜在机制。索拉非尼可减少ctcc移植小鼠肿瘤组织中MDSCs的数量,下调CX3CL1的表达。索拉非尼靶轴血管内皮生长因子A (VEGF-A)和血小板衍生生长因子bb (PDGF-BB)重组蛋白在cTCC细胞株中表达升高。此外,cTCC患者尿液中CX3CL1水平与VEGF-A水平呈正相关。这些结果表明VEGF-A信号可以调节CX3CL1的表达。接下来,我们分析了CX3CL1是否加速了MDSC的浸润。MDSCs表达CX3CL1受体CX3CR1,并以剂量依赖的方式向重组CX3CL1蛋白迁移。在ctcc移植小鼠模型中,CX3CL1缺失或CX3CR1抑制剂治疗显示出抗肿瘤作用,并减少肿瘤组织中的MDSCs。总的来说,我们的研究结果表明CX3CL1促进MDSC浸润,CX3CL1/CX3CR1轴可能是调节cTCC犬MDSCs的治疗靶点。
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引用次数: 0
Analysis of IgG responses to Sarcocystis neurona in horses with equine protozoal myeloencephalitis (EPM) suggests a Th1-biased immune response 马原生动物髓性脑炎(EPM)患者对神经元性肌囊炎的IgG应答分析表明存在th1偏向性免疫应答
IF 1.4 3区 农林科学 Q4 IMMUNOLOGY Pub Date : 2025-09-24 DOI: 10.1016/j.vetimm.2025.111009
Catherine J. Angwin , Izabela de Assis Rocha , Stephen M. Reed , Jennifer K. Morrow , Amy Graves , Daniel K. Howe
Equine protozoal myeloencephalitis (EPM) caused by Sarcocystis neurona is one of the most important neurological diseases of horses in the Americas. While seroprevalence of S. neurona in horses is high, clinical manifestation of EPM occurs in less than 1 % of infected horses. Antemortem diagnosis has proven challenging as serum antibodies against S. neurona are an indicator of infection but not necessarily disease. Factors governing the occurrence of EPM are largely unknown, although horse immunity might contribute to EPM pathogenesis. Immunoglobulin G is the predominant antibody class in equine serum and consists of four subisotypes; IgG1/2 (IgGa) and IgG4/7 (IgGb) are thought to be indicative of a Th1, cell-mediated immune response, and isotypes IgG3/5 (IgG(T)) and IgG6 (IgGc) are thought to be indicative of a Th2, humoral response. Herein, we examined the hypothesis that EPM occurs due to an aberrant immune response, which will be discernable by IgG subisotypes. A modified ELISA was used to quantify S. neurona antigen-specific IgG sub-isotypes 1/2, 3/5, and 4/7. Based on documented serum concentrations of IgG subisotypes, standard curves were generated using sera from 21 healthy horses and S. neurona-specific IgG subisotype levels were determined in serum and cerebrospinal spinal fluid from infected diseased (n = 93) and infected normal (n = 116) horses. The mean IgG3/5 serum concentration and IgG1/2:IgG3/5 ratio against S. neurona were found to be significantly different between diseased and normal horses, suggesting that the immune response to S. neurona in EPM horses is skewed towards a Th1, cell-mediated response. Unfortunately, these differences were not sufficient for developing a serum-based immunoassay for EPM diagnosis.
马原虫性髓脑炎(EPM)是美洲马最重要的神经系统疾病之一。虽然马的神经索菌血清阳性率很高,但只有不到1%的感染马出现EPM的临床表现。死前诊断已被证明是具有挑战性的,因为血清中抗神经索细胞抗体是感染的指标,但不一定是疾病。控制EPM发生的因素在很大程度上是未知的,尽管马的免疫可能有助于EPM的发病机制。免疫球蛋白G是马血清中主要的抗体类别,由四个亚型组成;IgG1/2 (IgGa)和IgG4/7 (IgGb)被认为是Th1细胞介导的免疫应答的指示,IgG3/5 (IgG(T))和IgG6 (IgGc)被认为是Th2体液应答的指示。在这里,我们检验了EPM是由于异常免疫反应而发生的假设,这将被IgG亚型所识别。采用改良的ELISA法定量神经索细胞抗原特异性IgG亚型1/2、3/5和4/7。根据记录的血清IgG亚型浓度,使用21匹健康马的血清生成标准曲线,并在感染病马(n = 93)和感染正常马(n = 116)的血清和脑脊液中测定神经元s特异性IgG亚型水平。病马与正常马血清中IgG3/5的平均浓度和IgG1/2:IgG3/5对神经索菌的比值存在显著差异,表明EPM马对神经索菌的免疫反应倾向于Th1细胞介导的应答。不幸的是,这些差异不足以开发基于血清的EPM诊断免疫分析。
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引用次数: 0
Analysis of IgG responses to Sarcocystis neurona in horses with equine protozoal myeloencephalitis (EPM) suggests a Th1-biased immune response 马原生动物髓性脑炎(EPM)患者对神经元性肌囊炎的IgG应答分析表明存在th1偏向性免疫应答
IF 1.4 3区 农林科学 Q4 IMMUNOLOGY Pub Date : 2025-09-24 DOI: 10.1016/j.vetimm.2025.111009
Catherine J. Angwin , Izabela de Assis Rocha , Stephen M. Reed , Jennifer K. Morrow , Amy Graves , Daniel K. Howe
Equine protozoal myeloencephalitis (EPM) caused by Sarcocystis neurona is one of the most important neurological diseases of horses in the Americas. While seroprevalence of S. neurona in horses is high, clinical manifestation of EPM occurs in less than 1 % of infected horses. Antemortem diagnosis has proven challenging as serum antibodies against S. neurona are an indicator of infection but not necessarily disease. Factors governing the occurrence of EPM are largely unknown, although horse immunity might contribute to EPM pathogenesis. Immunoglobulin G is the predominant antibody class in equine serum and consists of four subisotypes; IgG1/2 (IgGa) and IgG4/7 (IgGb) are thought to be indicative of a Th1, cell-mediated immune response, and isotypes IgG3/5 (IgG(T)) and IgG6 (IgGc) are thought to be indicative of a Th2, humoral response. Herein, we examined the hypothesis that EPM occurs due to an aberrant immune response, which will be discernable by IgG subisotypes. A modified ELISA was used to quantify S. neurona antigen-specific IgG sub-isotypes 1/2, 3/5, and 4/7. Based on documented serum concentrations of IgG subisotypes, standard curves were generated using sera from 21 healthy horses and S. neurona-specific IgG subisotype levels were determined in serum and cerebrospinal spinal fluid from infected diseased (n = 93) and infected normal (n = 116) horses. The mean IgG3/5 serum concentration and IgG1/2:IgG3/5 ratio against S. neurona were found to be significantly different between diseased and normal horses, suggesting that the immune response to S. neurona in EPM horses is skewed towards a Th1, cell-mediated response. Unfortunately, these differences were not sufficient for developing a serum-based immunoassay for EPM diagnosis.
马原虫性髓脑炎(EPM)是美洲马最重要的神经系统疾病之一。虽然马的神经索菌血清阳性率很高,但只有不到1%的感染马出现EPM的临床表现。死前诊断已被证明是具有挑战性的,因为血清中抗神经索细胞抗体是感染的指标,但不一定是疾病。控制EPM发生的因素在很大程度上是未知的,尽管马的免疫可能有助于EPM的发病机制。免疫球蛋白G是马血清中主要的抗体类别,由四个亚型组成;IgG1/2 (IgGa)和IgG4/7 (IgGb)被认为是Th1细胞介导的免疫应答的指示,IgG3/5 (IgG(T))和IgG6 (IgGc)被认为是Th2体液应答的指示。在这里,我们检验了EPM是由于异常免疫反应而发生的假设,这将被IgG亚型所识别。采用改良的ELISA法定量神经索细胞抗原特异性IgG亚型1/2、3/5和4/7。根据记录的血清IgG亚型浓度,使用21匹健康马的血清生成标准曲线,并在感染病马(n = 93)和感染正常马(n = 116)的血清和脑脊液中测定神经元s特异性IgG亚型水平。病马与正常马血清中IgG3/5的平均浓度和IgG1/2:IgG3/5对神经索菌的比值存在显著差异,表明EPM马对神经索菌的免疫反应倾向于Th1细胞介导的应答。不幸的是,这些差异不足以开发基于血清的EPM诊断免疫分析。
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引用次数: 0
Evaluation of pro-inflammatory activity and immunogenicity of an inactivated SBA-15 silica vaccine against Mycoplasma hyopneumoniae in piglets 猪肺炎支原体SBA-15灭活疫苗的促炎活性和免疫原性评价
IF 1.4 3区 农林科学 Q4 IMMUNOLOGY Pub Date : 2025-09-23 DOI: 10.1016/j.vetimm.2025.111008
Gabriel A. de Aguiar , Fernando A. Moreira Petri , Daniela G. da Silva , Marina L. Mechler-Dreibi , Tereza S. Martins , Márcia C.A. Fantini , Osvaldo A. Sant’Anna , Hélio J. Montassier , Luís Guilherme de Oliveira
Mycoplasma (M.) hyopneumoniae, the agent of porcine enzootic pneumonia (PEP), a primary pathogen of porcine respiratory disease complex (PRDC), reduces productivity and increases economic losses in swine production, with vaccination being the most important method to control the disease in the producing farms. This study evaluates the pro-inflammatory activity and immunogenicity of an inactivated vaccine for M. hyopneumoniae using an SBA-15 silica-based adjuvant in piglets. Forty-eight weaned piglets were divided into four groups (n = 12/group): a commercial vaccine group (CV); an SBA-15 adjuvanted vaccine group (SBA-15-Vac); a control group, receiving a suspension of SBA-15 with PBS, without the antigen (SBA-15-Cont), and a group that received saline solution (NV). SBA-15-Cont group served as a control for adjuvant-related effects, while the NV group served as negative control for lung lesion analysis, only. All animals were challenged, 21 days post vaccination, with M. hyopneumoniae strain 232. The evaluation of clinical signs was performed, and the inflammatory response was evaluated by measuring acute-phase proteins, as well as anti-M. hyopneumoniae IgG and IgA antibody levels. The SBA-15 adjuvant control group demonstrated mild inflammatory responses maintaining stable transferrin and haptoglobin levels after vaccination, suggesting a controlled inflammatory response compared to the commercial vaccine. The SBA-15 group exhibited a delayed but sustained immune response, suggesting a possible depot effect. Acute-phase protein levels, particularly ceruloplasmin and haptoglobin. Our findings support the potential of SBA-15 as a safe and effective adjuvant and highlight that SBA-15 silica nanoparticles are a promising and safe adjuvant in swine vaccines against M. hyopneumoniae.
猪肺炎支原体(M.)是猪地方性肺炎(PEP)的病原体,是猪呼吸道疾病复合体(PRDC)的主要病原体,它降低了猪生产的生产力,增加了猪生产的经济损失,疫苗接种是养猪场控制该病的最重要方法。本研究用SBA-15硅基佐剂对仔猪进行猪肺炎支原体灭活疫苗的促炎活性和免疫原性评价。48头断奶仔猪分为4组(n = 12头/组):商品疫苗组(CV);SBA-15佐剂疫苗组(SBA-15- vac);对照组接受不含抗原的PBS SBA-15悬液(SBA-15- cont),另一组接受生理盐水(NV)。SBA-15-Cont组作为佐剂相关效应的对照组,而NV组仅作为肺病变分析的阴性对照组。所有动物在接种疫苗后21天感染猪肺炎支原体菌株232。评估临床体征,并通过测定急性期蛋白和抗m。肺炎链球菌IgG和IgA抗体水平。SBA-15佐剂对照组在接种疫苗后表现出轻微的炎症反应,维持稳定的转铁蛋白和触珠蛋白水平,表明与商业疫苗相比,炎症反应受到控制。SBA-15组表现出延迟但持续的免疫反应,表明可能存在储存效应。急性期蛋白水平,特别是铜蓝蛋白和触珠蛋白。我们的研究结果支持SBA-15作为一种安全有效的佐剂的潜力,并强调SBA-15二氧化硅纳米颗粒是猪肺炎支原体疫苗中一种有前途的安全佐剂。
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引用次数: 0
Chronic in vitro heat with lipopolysaccharide stress differentially alters physiological response of Bos indicus and Bos taurus monocyte-derived macrophages 慢性体外热与脂多糖应激对牛和牛单核细胞源性巨噬细胞的生理反应有不同的改变
IF 1.4 3区 农林科学 Q4 IMMUNOLOGY Pub Date : 2025-09-23 DOI: 10.1016/j.vetimm.2025.111007
Kandasamy Rajamanickam , Visha Pasuvalingam , Elango Ayyasamy , Periyasamy Vijayakumar
The Bos taurus and Bos indicus cattle evolved in different climatic conditions, and they acquired various adaptive traits for their survival. This study unravels the impact of chronic in vitro thermal stress with lipopolysaccharide stress on functional responses of Bos indicus (Kangayam cattle) and Bos taurus (Jersey crossbred cattle) monocyte-derived macrophages. To achieve this, monocyte-derived macrophages from both cattle types were stimulated with lipopolysaccharide (1.0 μg/mL) at either 37°C or 40°C for 24 and 48 h, and their cellular and immune responses were evaluated. The results revealed that Bos indicus monocyte-derived macrophages exhibit enhanced cell viability, oxidative and phagocytosis functions, as well as improved autophagy response to lipopolysaccharide stimulation during thermal stress. Additionally, Bos indicus monocyte-derived macrophages demonstrated reduced variability in transcription of genes related to heat shock, cell signalling, and inflammatory cytokines compared to Bos taurus. Factors such as breed, thermal and lipopolysaccharide stress, period of stress exposure, and their interactions have a significant impact on cellular and immune functions of monocyte-derived macrophages. In conclusion, the monocyte-derived macrophages of Bos indicus possess an enhanced immune-thermal resilience property than Bos taurus.
牛牛和印度牛牛在不同的气候条件下进化,获得了各种适应生存的特征。本研究揭示了体外慢性热应激和脂多糖应激对康亚姆牛(Bos indicus)和泽西杂交牛(Bos taurus)单核细胞源性巨噬细胞功能的影响。为了实现这一目标,用脂多糖(1.0 μg/mL)在37°C或40°C下刺激两种牛的单核细胞来源的巨噬细胞24和48 h,并评估它们的细胞和免疫反应。结果表明,在热应激条件下,红鲌单核细胞来源的巨噬细胞表现出增强的细胞活力、氧化和吞噬功能,以及对脂多糖刺激的自噬反应。此外,与牛Bos相比,牛Bos indicus单核细胞来源的巨噬细胞表现出与热休克、细胞信号传导和炎症细胞因子相关的基因转录变异性降低。品种、热应激和脂多糖应激、应激暴露时间及其相互作用等因素对单核细胞源性巨噬细胞的细胞和免疫功能有显著影响。综上所述,印度水牛单核细胞来源的巨噬细胞比牛具有更强的免疫热恢复能力。
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引用次数: 0
Chronic in vitro heat with lipopolysaccharide stress differentially alters physiological response of Bos indicus and Bos taurus monocyte-derived macrophages 慢性体外热与脂多糖应激对牛和牛单核细胞源性巨噬细胞的生理反应有不同的改变
IF 1.4 3区 农林科学 Q4 IMMUNOLOGY Pub Date : 2025-09-23 DOI: 10.1016/j.vetimm.2025.111007
Kandasamy Rajamanickam , Visha Pasuvalingam , Elango Ayyasamy , Periyasamy Vijayakumar
The Bos taurus and Bos indicus cattle evolved in different climatic conditions, and they acquired various adaptive traits for their survival. This study unravels the impact of chronic in vitro thermal stress with lipopolysaccharide stress on functional responses of Bos indicus (Kangayam cattle) and Bos taurus (Jersey crossbred cattle) monocyte-derived macrophages. To achieve this, monocyte-derived macrophages from both cattle types were stimulated with lipopolysaccharide (1.0 μg/mL) at either 37°C or 40°C for 24 and 48 h, and their cellular and immune responses were evaluated. The results revealed that Bos indicus monocyte-derived macrophages exhibit enhanced cell viability, oxidative and phagocytosis functions, as well as improved autophagy response to lipopolysaccharide stimulation during thermal stress. Additionally, Bos indicus monocyte-derived macrophages demonstrated reduced variability in transcription of genes related to heat shock, cell signalling, and inflammatory cytokines compared to Bos taurus. Factors such as breed, thermal and lipopolysaccharide stress, period of stress exposure, and their interactions have a significant impact on cellular and immune functions of monocyte-derived macrophages. In conclusion, the monocyte-derived macrophages of Bos indicus possess an enhanced immune-thermal resilience property than Bos taurus.
牛牛和印度牛牛在不同的气候条件下进化,获得了各种适应生存的特征。本研究揭示了体外慢性热应激和脂多糖应激对康亚姆牛(Bos indicus)和泽西杂交牛(Bos taurus)单核细胞源性巨噬细胞功能的影响。为了实现这一目标,用脂多糖(1.0 μg/mL)在37°C或40°C下刺激两种牛的单核细胞来源的巨噬细胞24和48 h,并评估它们的细胞和免疫反应。结果表明,在热应激条件下,红鲌单核细胞来源的巨噬细胞表现出增强的细胞活力、氧化和吞噬功能,以及对脂多糖刺激的自噬反应。此外,与牛Bos相比,牛Bos indicus单核细胞来源的巨噬细胞表现出与热休克、细胞信号传导和炎症细胞因子相关的基因转录变异性降低。品种、热应激和脂多糖应激、应激暴露时间及其相互作用等因素对单核细胞源性巨噬细胞的细胞和免疫功能有显著影响。综上所述,印度水牛单核细胞来源的巨噬细胞比牛具有更强的免疫热恢复能力。
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引用次数: 0
Evaluation of pro-inflammatory activity and immunogenicity of an inactivated SBA-15 silica vaccine against Mycoplasma hyopneumoniae in piglets 猪肺炎支原体SBA-15灭活疫苗的促炎活性和免疫原性评价
IF 1.4 3区 农林科学 Q4 IMMUNOLOGY Pub Date : 2025-09-23 DOI: 10.1016/j.vetimm.2025.111008
Gabriel A. de Aguiar , Fernando A. Moreira Petri , Daniela G. da Silva , Marina L. Mechler-Dreibi , Tereza S. Martins , Márcia C.A. Fantini , Osvaldo A. Sant’Anna , Hélio J. Montassier , Luís Guilherme de Oliveira
Mycoplasma (M.) hyopneumoniae, the agent of porcine enzootic pneumonia (PEP), a primary pathogen of porcine respiratory disease complex (PRDC), reduces productivity and increases economic losses in swine production, with vaccination being the most important method to control the disease in the producing farms. This study evaluates the pro-inflammatory activity and immunogenicity of an inactivated vaccine for M. hyopneumoniae using an SBA-15 silica-based adjuvant in piglets. Forty-eight weaned piglets were divided into four groups (n = 12/group): a commercial vaccine group (CV); an SBA-15 adjuvanted vaccine group (SBA-15-Vac); a control group, receiving a suspension of SBA-15 with PBS, without the antigen (SBA-15-Cont), and a group that received saline solution (NV). SBA-15-Cont group served as a control for adjuvant-related effects, while the NV group served as negative control for lung lesion analysis, only. All animals were challenged, 21 days post vaccination, with M. hyopneumoniae strain 232. The evaluation of clinical signs was performed, and the inflammatory response was evaluated by measuring acute-phase proteins, as well as anti-M. hyopneumoniae IgG and IgA antibody levels. The SBA-15 adjuvant control group demonstrated mild inflammatory responses maintaining stable transferrin and haptoglobin levels after vaccination, suggesting a controlled inflammatory response compared to the commercial vaccine. The SBA-15 group exhibited a delayed but sustained immune response, suggesting a possible depot effect. Acute-phase protein levels, particularly ceruloplasmin and haptoglobin. Our findings support the potential of SBA-15 as a safe and effective adjuvant and highlight that SBA-15 silica nanoparticles are a promising and safe adjuvant in swine vaccines against M. hyopneumoniae.
猪肺炎支原体(M.)是猪地方性肺炎(PEP)的病原体,是猪呼吸道疾病复合体(PRDC)的主要病原体,它降低了猪生产的生产力,增加了猪生产的经济损失,疫苗接种是养猪场控制该病的最重要方法。本研究用SBA-15硅基佐剂对仔猪进行猪肺炎支原体灭活疫苗的促炎活性和免疫原性评价。48头断奶仔猪分为4组(n = 12头/组):商品疫苗组(CV);SBA-15佐剂疫苗组(SBA-15- vac);对照组接受不含抗原的PBS SBA-15悬液(SBA-15- cont),另一组接受生理盐水(NV)。SBA-15-Cont组作为佐剂相关效应的对照组,而NV组仅作为肺病变分析的阴性对照组。所有动物在接种疫苗后21天感染猪肺炎支原体菌株232。评估临床体征,并通过测定急性期蛋白和抗m。肺炎链球菌IgG和IgA抗体水平。SBA-15佐剂对照组在接种疫苗后表现出轻微的炎症反应,维持稳定的转铁蛋白和触珠蛋白水平,表明与商业疫苗相比,炎症反应受到控制。SBA-15组表现出延迟但持续的免疫反应,表明可能存在储存效应。急性期蛋白水平,特别是铜蓝蛋白和触珠蛋白。我们的研究结果支持SBA-15作为一种安全有效的佐剂的潜力,并强调SBA-15二氧化硅纳米颗粒是猪肺炎支原体疫苗中一种有前途的安全佐剂。
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引用次数: 0
Characterization of genital system inflammatory response in female dogs naturally infected with Leishmania infantum* 自然感染幼年利什曼原虫的母犬生殖系统炎症反应的特征*
IF 1.4 3区 农林科学 Q4 IMMUNOLOGY Pub Date : 2025-09-20 DOI: 10.1016/j.vetimm.2025.111006
Paulo Henrique Leal Bertolo , Maria Eduarda Bastos Andrade Moutinho da Conceição , Pamela Rodrigues Reina Moreira , Beatriz Cristiane Mioto , Rafael Rocha Mello Emboaba da Costa , Fernanda Ramalho Ramos , Bethânia Almeida Gouveia , Maricy Apparíccio Ferreira , Daniela Bernadete Rozza , Rosemeri de Oliveira Vasconcelos
The genital system of female dogs with visceral leishmaniasis (VL) commonly shows lesions on the external genitalia (vulva and vagina). This study aimed to evaluate the inflammatory response in segments of the reproductive tract of female dogs naturally infected with Leishmania infantum, and to correlate these findings with hormonal status (high or low progesterone levels), local parasitism, and local inflammatory infiltrate immunophenotype. Sixteen unspayed, non-pregnant adult female dogs naturally infected with L. infantum, without any other disease, were used. Animals were divided into two groups: G1 (n = 5, high-progesterone phase) and G2 (n = 11, low-progesterone phase). Parasite presence and the immunophenotype of leukocytes infiltrating the genital system (CD3, CD4, CD8, and MCA874) were determined by immunohistochemistry. Chronic inflammatory infiltrate was the predominant lesion and was mainly found in the vulva and vagina. Internal genitalia segments (cervix, uterus, ovary) presented fewer lesions. Animals of G1 group exhibited higher number of immunolabeled parasites in the internal segments of the reproductive tract and of cells positive for CD3 (T lymphocytes) and MCA874 (macrophages) than G2 group. There was no difference for CD4 and CD8 between groups. However, multivariate analysis showed positive correlations with T lymphocyte subtypes, macrophages, and parasite presence in different segments of the reproductive tract of G1 animals. Leukocyte population and number of parasitized cells in the reproductive tract increased with escalating progesterone levels (G1 group), suggesting that estrus and diestrus stages are most favorable to infection maintenance.
患有内脏利什曼病(VL)的母狗的生殖系统通常在外生殖器(外阴和阴道)上显示病变。本研究旨在评估自然感染婴儿利什曼原虫的母狗生殖道部分的炎症反应,并将这些发现与激素状态(高或低孕酮水平)、局部寄生和局部炎症浸润免疫表型相关联。16只未绝育、未怀孕的成年母狗自然感染了婴儿乳杆菌,没有任何其他疾病。将动物分为两组:G1组(n = 5,高孕酮期)和G2组(n = 11,低孕酮期)。通过免疫组织化学检测寄生虫的存在和浸润生殖系统白细胞的免疫表型(CD3、CD4、CD8和MCA874)。慢性炎症浸润是主要病变,主要见于外阴和阴道。内生殖器(子宫颈、子宫、卵巢)病变较少。G1组动物生殖道内段免疫标记的寄生虫数量和CD3 (T淋巴细胞)和MCA874(巨噬细胞)阳性细胞数量均高于G2组。各组间CD4和CD8水平无差异。然而,多变量分析显示,G1动物生殖道不同节段的T淋巴细胞亚型、巨噬细胞和寄生虫的存在正相关。生殖道内白细胞数量和被寄生细胞数量随着孕酮水平的升高而增加(G1组),提示发情期和退情期最有利于感染维持。
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引用次数: 0
Characterization of genital system inflammatory response in female dogs naturally infected with Leishmania infantum* 自然感染幼年利什曼原虫的母犬生殖系统炎症反应的特征*
IF 1.4 3区 农林科学 Q4 IMMUNOLOGY Pub Date : 2025-09-20 DOI: 10.1016/j.vetimm.2025.111006
Paulo Henrique Leal Bertolo , Maria Eduarda Bastos Andrade Moutinho da Conceição , Pamela Rodrigues Reina Moreira , Beatriz Cristiane Mioto , Rafael Rocha Mello Emboaba da Costa , Fernanda Ramalho Ramos , Bethânia Almeida Gouveia , Maricy Apparíccio Ferreira , Daniela Bernadete Rozza , Rosemeri de Oliveira Vasconcelos
The genital system of female dogs with visceral leishmaniasis (VL) commonly shows lesions on the external genitalia (vulva and vagina). This study aimed to evaluate the inflammatory response in segments of the reproductive tract of female dogs naturally infected with Leishmania infantum, and to correlate these findings with hormonal status (high or low progesterone levels), local parasitism, and local inflammatory infiltrate immunophenotype. Sixteen unspayed, non-pregnant adult female dogs naturally infected with L. infantum, without any other disease, were used. Animals were divided into two groups: G1 (n = 5, high-progesterone phase) and G2 (n = 11, low-progesterone phase). Parasite presence and the immunophenotype of leukocytes infiltrating the genital system (CD3, CD4, CD8, and MCA874) were determined by immunohistochemistry. Chronic inflammatory infiltrate was the predominant lesion and was mainly found in the vulva and vagina. Internal genitalia segments (cervix, uterus, ovary) presented fewer lesions. Animals of G1 group exhibited higher number of immunolabeled parasites in the internal segments of the reproductive tract and of cells positive for CD3 (T lymphocytes) and MCA874 (macrophages) than G2 group. There was no difference for CD4 and CD8 between groups. However, multivariate analysis showed positive correlations with T lymphocyte subtypes, macrophages, and parasite presence in different segments of the reproductive tract of G1 animals. Leukocyte population and number of parasitized cells in the reproductive tract increased with escalating progesterone levels (G1 group), suggesting that estrus and diestrus stages are most favorable to infection maintenance.
患有内脏利什曼病(VL)的母狗的生殖系统通常在外生殖器(外阴和阴道)上显示病变。本研究旨在评估自然感染婴儿利什曼原虫的母狗生殖道部分的炎症反应,并将这些发现与激素状态(高或低孕酮水平)、局部寄生和局部炎症浸润免疫表型相关联。16只未绝育、未怀孕的成年母狗自然感染了婴儿乳杆菌,没有任何其他疾病。将动物分为两组:G1组(n = 5,高孕酮期)和G2组(n = 11,低孕酮期)。通过免疫组织化学检测寄生虫的存在和浸润生殖系统白细胞的免疫表型(CD3、CD4、CD8和MCA874)。慢性炎症浸润是主要病变,主要见于外阴和阴道。内生殖器(子宫颈、子宫、卵巢)病变较少。G1组动物生殖道内段免疫标记的寄生虫数量和CD3 (T淋巴细胞)和MCA874(巨噬细胞)阳性细胞数量均高于G2组。各组间CD4和CD8水平无差异。然而,多变量分析显示,G1动物生殖道不同节段的T淋巴细胞亚型、巨噬细胞和寄生虫的存在正相关。生殖道内白细胞数量和被寄生细胞数量随着孕酮水平的升高而增加(G1组),提示发情期和退情期最有利于感染维持。
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引用次数: 0
Expanding tropism: Avian B cells as novel cellular target of infectious bronchitis virus 趋向性扩展:禽B细胞是传染性支气管炎病毒的新细胞靶点。
IF 1.4 3区 农林科学 Q4 IMMUNOLOGY Pub Date : 2025-09-18 DOI: 10.1016/j.vetimm.2025.111005
Sufna M. Suhail, Motamed E. Mahmoud, Ishara M. Isham, Ahmed Ali, Muhammad Farooq, Anne Shehara Perera, Lahiru W. Waduge, Luke Xiu, Susan C. Cork, Ashish Gupta, Mohamed Faizal Abdul-Careem
Infectious bronchitis virus (IBV) causes infectious bronchitis (IB), which is a major concern for the global poultry industry as a result of substantial economic losses. Although epithelial cells were described as the primary target cells of IBV, other susceptible cell types including macrophages and monocytes, have been identified, where productive infection impairs cellular functions. Avian B cells are central to antibody-mediated immunity in chickens against pathogens, including IBV; however, it remains unknown if IBV can infect and replicate in B cells. This study investigated whether Delmarva (DMV)/1639 IBV can infect B cells in the bursa of Fabricius (BF) in vivo and in DT–40 cells in vitro. In vivo, a significantly higher viral genome load was observed in the BF at 3 days post-infection (dpi), with similar result in sorted B cells from the BF. Viral RNA was found to be localized within B cells of the BF using an in situ hybridization combined with immunohistochemistry. In vitro, a comparable trend in viral genome load was observed in infected DT–40 cells and culture supernatants up to 72 h post-infection (hpi). Immunofluorescence assay revealed a significantly higher percentage of DT–40 cells expressing IBV nucleoprotein. Inoculation of DT-40 cells with virus-containing supernatant confirmed infectivity as did inoculation of embryonated eggs, which resulted in IBV-specific lesions including dwarfing and stunting. These findings demonstrate that IBV can infect and replicate productively in avian B cells; however further studies are warranted to elucidate the impact of IBV infection on B cell function and its role in disease pathogenesis.
传染性支气管炎病毒(IBV)引起传染性支气管炎(IB),这是全球家禽业关注的一个主要问题,造成了巨大的经济损失。虽然上皮细胞被描述为IBV的主要靶细胞,但其他易感细胞类型,包括巨噬细胞和单核细胞,已被确定,其中生产性感染损害细胞功能。禽B细胞是鸡对病原体(包括IBV)的抗体介导免疫的核心;然而,IBV是否能感染B细胞并在B细胞中复制尚不清楚。本实验研究了Delmarva (DMV)/1639 IBV是否能在体内感染法氏囊(BF) B细胞,并在体外感染DT-40细胞。在体内,在感染后3天(dpi), BF中观察到明显更高的病毒基因组载量,从BF中分类的B细胞也有类似的结果。利用原位杂交结合免疫组化技术,发现病毒RNA在BF的B细胞内定位。在体外,在感染后72 h (hpi)感染的DT-40细胞和培养上清中观察到病毒基因组负荷的类似趋势。免疫荧光分析显示,表达IBV核蛋白的DT-40细胞比例显著提高。用含病毒的上清液接种DT-40细胞证实了感染能力,接种胚卵也证实了感染能力,导致ibv特异性病变,包括矮化和发育迟缓。这些结果表明,IBV可以感染并在禽B细胞中高效复制;然而,IBV感染对B细胞功能的影响及其在疾病发病机制中的作用有待进一步研究。
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引用次数: 0
期刊
Veterinary immunology and immunopathology
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