Regulatory B cell (B10 Cell) expansion during Listeria infection governs innate and cellular immune responses in mice.
Regulatory B cell (B10 Cell) expansion during Listeria infection governs innate and cellular immune responses in mice.
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DOI：
10.4049/jimmunol.1201427
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发表时间：
2013-02-01
期刊：
影响因子：
--
通讯作者：
Tedder TF
中科院分区：
文献类型：
--
作者：
Horikawa M;Weimer ET;DiLillo DJ;Venturi GM;Spolski R;Leonard WJ;Heise MT;Tedder TF
病原体使用多种方法来破坏宿主的免疫反应，包括通过不同细胞类型调节宿主IL-10的产生。然而，在感染期间，IL-10的B细胞来源及其对先天和细胞免疫反应的总体影响尚未得到很好的表征。以李斯特菌为模型病原体，感染驱动一小部分调节性B细胞（B10细胞）的急性扩增，这些细胞通过产生IL-10有效地抑制炎症和自身免疫。出乎意料的是，在B10细胞缺乏的CD19−/−小鼠中，在成熟B细胞缺失的小鼠中，以及在感染前用CD22 mAb处理以优先消耗B10细胞的小鼠中，脾脏细菌负荷降低了92-97%。相比之下，野生型B10细胞的过继转移通过il -10依赖途径使CD19−/−小鼠的细菌清除率降低了38倍。CD22单抗可显著增强李斯特菌的巨噬细胞吞噬能力及其体外IFN-γ、TNF-α和一氧化氮的产生。B10细胞耗竭后加速细菌清除可显著降低ag特异性CD4+ T细胞增殖和细胞因子产生，但不改变CD8+ T细胞反应。尽管如此，先天免疫应答中的B10细胞调节功能依赖于与CD4+ T细胞的同源相互作用，因为缺乏IL-10、MHC-II或IL-21受体表达的B10细胞并不影响李斯特菌的清除。因此，李斯特菌通过免疫逃避策略操纵免疫应答，该策略涉及内源性B10细胞的优先扩张，该细胞调节先天和细胞免疫应答的大小和持续时间。
Pathogens use numerous methods to subvert host immune responses, including the modulation of host IL-10 production by diverse cell types. However, the B cell sources of IL-10 and their overall influence on innate and cellular immune responses have not been well characterized during infections. Using Listeria as a model pathogen, infection drove the acute expansion of a small subset of regulatory B cells (B10 cells) that potently suppress inflammation and autoimmunity through the production of IL-10. Unexpectedly, spleen bacteria loads were 92–97% lower in B10 cell-deficient CD19−/− mice, in mice depleted of mature B cells, and in mice treated with CD22 mAb to preferentially deplete B10 cells before infection. By contrast, the adoptive transfer of wild type B10 cells reduced bacterial clearance by 38-fold in CD19−/− mice through IL-10-dependent pathways. B10 cell depletion using CD22 mAb significantly enhanced macrophage phagocytosis of Listeria and their production of IFN-γ, TNF-α, and nitric oxide ex vivo. Accelerated bacteria clearance following B10 cell depletion significantly reduced Ag-specific CD4+ T cell proliferation and cytokine production, but did not alter CD8+ T cell responses. B10 cell regulatory function during innate immune responses was nonetheless dependent on cognate interactions with CD4+ T cells since B10 cells deficient in IL-10, MHC-II or IL-21 receptor expression did not influence Listeria clearance. Thus, Listeria manipulates immune responses through a strategy of immune evasion that involves the preferential expansion of endogenous B10 cells that regulate the magnitude and duration of both innate and cellular immune responses.
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DOI：
10.1084/jem.20101715
发表时间：
2011-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kelly-Scumpia KM;Scumpia PO;Weinstein JS;Delano MJ;Cuenca AG;Nacionales DC;Wynn JL;Lee PY;Kumagai Y;Efron PA;Akira S;Wasserfall C;Atkinson MA;Moldawer LL
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