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首页> 外文期刊>Infection and immunity >Myeloid Differentiation Antigen 88 Deficiency Impairs Pathogen Clearance but Does Not Alter Inflammation in Borrelia burgdorferi-Infected Mice
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Myeloid Differentiation Antigen 88 Deficiency Impairs Pathogen Clearance but Does Not Alter Inflammation in Borrelia burgdorferi-Infected Mice

机译：髓样分化抗原88缺陷会损害病原体清除，但不会改变伯氏疏螺旋体感染小鼠的炎症。

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The spirochete Borrelia burgdorferi causes acute inflammation in mice that resolves with the development of pathogen-specific adaptive immunity. B. burgdorferi lipoproteins activate innate immune cells via Toll-like receptor 2 (TLR2), but TLR2-deficient mice are not resistant to B. burgdorferi-induced disease, suggesting the involvement of other TLRs or non-TLR mechanisms in the induction of acute inflammation. For this study, we used mice that were deficient in the intracellular adapter molecule myeloid differentiation antigen 88 (MyD88), which is required for all TLR-induced inflammatory responses, to determine whether the interruption of this pathway would alter B. burgdorferi-induced disease. Infected MyD88?/? mice developed carditis and arthritis, similar to the disease in wild-type (WT) mice analyzed at its peak (days 14 and 28) and during regression (day 45). MyD88?/? macrophages produced tumor necrosis factor alpha only when spirochetes were opsonized, suggesting a role for B. burgdorferi-specific antibody in disease expression. MyD88?/? mice produced stronger pathogen-specific Th2-dependent immunoglobulin G1 (IgG1) responses than did WT mice, and their IgM titers remained significantly elevated through 90 days of infection. Despite specific antibodies, the pathogen burden was 250-fold higher in MyD88?/? mice than in WT mice 45 days after infection; by 90 days of infection, the pathogen burden had diminished substantially in MyD88?/? mice, but it was still elevated compared to that in WT mice. The elevated pathogen burden may be explained in part by the finding that MyD88?/? peritoneal macrophages could ingest spirochetes but degraded them more slowly than WT macrophages. Our results show that MyD88-dependent signaling pathways are not required for B. burgdorferi-induced inflammation but are necessary for the efficient control of the pathogen burden by phagocytes.
机译：螺旋体 Borrelia burgdorferi 引起小鼠急性炎症，随着病原体特异性适应性免疫的发展而消退。 B。 burgdorferi脂蛋白通过Toll样受体2（TLR2）激活先天免疫细胞，但TLR2缺陷型小鼠对 B没有抵抗力。 burgdorferi引起的疾病，表明其他TLR或非TLR机制参与了急性炎症的诱导。在这项研究中，我们使用了缺乏细胞内衔接子分子髓样分化抗原88（MyD88）的小鼠，以确定该途径是否会改变 B，这是所有TLR诱导的炎症反应所必需的。伯氏病引起的疾病。感染的MyD88 α/β小鼠发展成心脏病和关节炎，类似于在高峰期（第14天和第28天）和回归期（第45天）分析的野生型（WT）小鼠的疾病。 MyD88 ？/？巨噬细胞仅在螺旋体被调理后才产生肿瘤坏死因子α，这提示了 B的作用。 burgdorferi特异性抗体在疾病表达中的作用。 MyD88 ？/？小鼠比野生型小鼠产生更强的病原体特异性Th2依赖性免疫球蛋白G1（IgG1）反应，并且在感染90天后其IgM滴度仍显着升高。尽管有特异性抗体，但感染后45天，MyD88 ？/？小鼠的病原体负担比WT小鼠高250倍。感染90天后，MyD88 ？/？小鼠的病原体负担已大大减少，但与WT小鼠相比，病原体负担仍在增加。病原体负担增加的部分原因可能是由于发现MyD88 α/？腹膜巨噬细胞可摄取螺旋体，但降解速度却比WT巨噬细胞慢。我们的结果表明， B不需要依赖MyD88的信号通路。 burgdorferi引起的炎症，但对于吞噬细胞有效控制病原体负担是必需的。

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