Li Lin-Xi, Labuda Jasmine C, Imai Denise M, Griffey Stephen M, McSorley Stephen J
Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, AR 72205;
Center for Comparative Medicine, Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616; and.
J Immunol. 2017 Oct 1;199(7):2547-2554. doi: 10.4049/jimmunol.1601314. Epub 2017 Aug 11.
Immune mechanisms responsible for pathogen clearance from the female reproductive tract (FRT) are incompletely defined; in particular, the contribution of lymphocyte trafficking to this process is unclear. CCR7-deficient mice have profoundly altered lymphocyte recirculation and display ectopic formation of lymphocyte aggregates within mucosal nonlymphoid tissues, including the FRT. In this study, we investigated how altered lymphocyte distribution in CCR7-deficient mice would affect host responses to within the reproductive tract. As expected, CCR7-deficient mice exhibited reduced lymphocyte trafficking to lymph nodes and a corresponding increase in T cell populations within the FRT. After intravaginal infection with , CCR7-deficient mice displayed markedly reduced Ag-specific CD4 T cell responses within the local draining iliac lymph nodes, yet robust Th1 and Th17 responses were prominent in the FRT. In addition, -specific Ab responses were dysregulated in CCR7-deficient mice, displaying an unexpected increase in the systemic IgA responses. Importantly, prominent mucosal immune responses in CCR7-deficient mice increased the efficiency of bacteria clearance from the FRT while reducing tissue-associated inflammation and pathology. Thus, increased numbers of lymphocytes within the FRT result in pathogen clearance with reduced immune-mediated pathology.
负责从女性生殖道(FRT)清除病原体的免疫机制尚未完全明确;尤其是淋巴细胞运输对这一过程的作用尚不清楚。CCR7缺陷小鼠的淋巴细胞再循环发生了深刻改变,并在包括FRT在内的黏膜非淋巴组织中出现淋巴细胞聚集的异位形成。在本研究中,我们调查了CCR7缺陷小鼠中改变的淋巴细胞分布如何影响生殖道内的宿主对[病原体名称未给出]的反应。正如预期的那样,CCR7缺陷小鼠表现出淋巴细胞向淋巴结的运输减少,以及FRT内T细胞群体相应增加。经阴道感染[病原体名称未给出]后,CCR7缺陷小鼠在局部引流的髂淋巴结内显示出明显降低的抗原特异性CD4 T细胞反应,但在FRT中强大的Th1和Th17反应却很突出。此外,CCR7缺陷小鼠中的[病原体名称未给出]特异性抗体反应失调,全身IgA反应意外增加。重要的是,CCR7缺陷小鼠中突出的黏膜免疫反应提高了从FRT清除细菌的效率,同时减少了组织相关的炎症和病理变化。因此,FRT内淋巴细胞数量增加导致病原体清除,同时免疫介导的病理变化减少。