Leishmania pifanoi pathogenesis:: Selective lack of a local cutaneous response in the absence of circulating antibody
Leishmania pifanoi pathogenesis:: Selective lack of a local cutaneous response in the absence of circulating antibody
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DOI：
10.1128/iai.70.12.6597-6605.2002
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发表时间：
2002-12-01
影响因子：
3.1
通讯作者：
McMahon-Pratt, D
中科院分区：
文献类型：
--
作者：
Colmenares, M;Constant, SL;McMahon-Pratt, D
最近，B细胞在利什曼原虫（墨西哥利什曼原虫复合体和L. Donovani）成立。在L。mexicana complex parasites（L.墨西哥湖（L. pifanoi和L. amazonensis），免疫球蛋白G介导的机制在宿主中无鞭毛体阶段的关键作用是明显的;然而，所涉及的免疫机制仍有待建立。在体外分析寄生虫吸收的动力学巨噬细胞未能表明抗体调理作用的主要影响。鉴于CD 4（+）T细胞在这些寄生虫引起的疾病发展中的重要性，探索了缺乏发病机制是由于局部部位（引流淋巴结和/或皮肤部位）缺乏免疫应答的可能性。有趣的是，在感染后2周、5周和10周，缺乏循环抗体的小鼠（耐药）引流淋巴结中的CD 4（+）-T细胞活化（增殖和细胞因子）水平与野生型小鼠（易感）的淋巴结相当。然而，与野生型小鼠相比，抗体缺陷动物在皮肤感染部位募集或保留的单核细胞和淋巴细胞数量显著减少，表明局部皮肤免疫应答的选择性损害。采用组织来源的（调理）无鞭毛体进行的体外抗原提呈研究表明，L。pifanoi感染的FcR（-/-）巨噬细胞，与pifanoi感染的野生型细胞相反，不能激活利什曼原虫抗原特异性T淋巴细胞。这些数据，综合起来，表明抗体在发病机制中的作用的一种可能的机制可能是介导寄生虫摄取和调节局部皮肤感染部位的免疫应答。
Recently, a role for B cells in the pathogenesis associated with infection by Leishmania (Leishmania mexicana complex and L. donovani) has been established. In the case of L. mexicana complex parasites (L. mexicana, L. pifanoi, and L. amazonensis), a critical role for immunoglobulin G-mediated mechanisms for the amastigote stage in the host is evident; however, the immunological mechanisms involved remain to be established. In vitro analysis of the kinetics of parasite uptake by macrophages failed to indicate a major effect of antibody opsonization. Given the importance of CD4(+) T cells in the development of disease caused by these parasites, the possibility that the lack of pathogenesis was due to the lack of development of an immune response at the local site (draining lymph node and/or cutaneous site) was explored. Interestingly, the level of CD4(+)-T-cell activation (proliferation and cytokine) in draining lymph nodes from mice lacking circulating antibody (resistant) was found to be comparable to that in nodes from wild-type mice (susceptible) at 2, 5, and 10 weeks postinfection. However, antibody-deficient animals had markedly reduced numbers of monocytes and lymphocytes recruited or retained at the site of cutaneous infection in comparison to wild-type mice, indicating a selective impairment in the local cutaneous immune response. In vitro antigen presentation studies employing tissue-derived (opsonized) amastigotes demonstrated that L. pifanoi-infected FcR(-/-) macrophages, in contrast to comparably infected wild-type cells, failed to activate Leishmania antigen-specific T lymphocytes. These data, taken together, suggest that one possible mechanism for the role of antibody in pathogenesis may be to mediate parasite uptake and regulate the immune response at the local cutaneous site of infection.