Signaling via the MyD88 Adaptor Protein in B Cells Suppresses Protective Immunity during Salmonella typhimurium Infection
Signaling via the MyD88 Adaptor Protein in B Cells Suppresses Protective Immunity during Salmonella typhimurium Infection
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DOI：
10.1016/j.immuni.2010.10.016
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发表时间：
2010-11-24
期刊：
影响因子：
32.4
通讯作者：
Fillatreau, Simon
中科院分区：
文献类型：
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作者：
Neves, Patricia;Lampropoulou, Vicky;Fillatreau, Simon
髓样分化初级应答基因88（Myd 88）对于抵抗病原体的保护至关重要。然而，我们在这里证明，MyD 88在B细胞中的表达抑制小鼠对鼠伤寒沙门氏菌感染的抵抗力。B细胞中Myd 88的选择性缺陷改善了对细菌复制的控制，并延长了受感染小鼠的存活时间。二次攻击后，B细胞介导的抑制途径更加显著。接种后，B细胞中缺乏Myd 88的小鼠变得对这种致命感染完全具有抗性，而对照小鼠仅受到部分保护。对免疫防御的分析显示，B细胞中的MyD 88信号转导抑制了保护性免疫的三个关键分支：中性粒细胞、自然杀伤细胞和炎性T细胞。我们进一步表明，白细胞介素-10是这些B细胞的抑制功能的重要介质。总的来说，我们的数据确定了MyD 88和B细胞在感染期间保护性免疫的细胞机制调节中的作用。
The myeloid differentiation primary response gene 88 (Myd88) is critical for protection against pathogens. However, we demonstrate here that MyD88 expression in B cells inhibits resistance of mice to Salmonella typhimurium infection. Selective deficiency of Myd88 in B cells improved control of bacterial replication and prolonged survival of the infected mice. The B cell-mediated suppressive pathway was even more striking after secondary challenge. Upon vaccination, mice lacking Myd88 in B cells became completely resistant against this otherwise lethal infection, whereas control mice were only partially protected. Analysis of immune defenses revealed that MyD88 signaling in B cells suppressed three crucial arms of protective immunity: neutrophils, natural killer cells, and inflammatory T cells. We further show that interleukin-10 is an essential mediator of these inhibitory functions of B cells. Collectively, our data identify a role for MyD88 and B cells in regulation of cellular mechanisms of protective immunity during infection.