Cutting Edge: The BTLA-HVEM Regulatory Pathway Interferes with Protective Immunity to Intestinal Helminth Infection
Cutting Edge: The BTLA-HVEM Regulatory Pathway Interferes with Protective Immunity to Intestinal Helminth Infection
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DOI：
10.4049/jimmunol.1402510
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发表时间：
2015-02-15
影响因子：
4.4
通讯作者：
Jacobs, Thomas
中科院分区：
文献类型：
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作者：
Breloer, Minka;Hartmann, Wiebke;Jacobs, Thomas
蠕虫利用哺乳动物免疫系统的内在调节途径来抑制针对它们的免疫应答。在这篇文章中，我们发现，感染寄生线虫类圆线虫诱导上调共抑制受体B和T淋巴细胞衰减因子（BTLA）主要在CD 4（+）T细胞，但也对一小部分的先天性白细胞。BTLA或其配体疱疹病毒进入介质（HVEM）的缺陷导致小肠中的寄生虫成虫数量减少，并在整个感染过程中减少幼虫输出。BTLA和HVEM缺陷小鼠的寄生虫负荷降低，伴随着粘膜肥大细胞的加速脱粒和肥大细胞活化细胞因子IL-9的Ag特异性产生增加。我们的综合结果支持一种模型，即CD 4（+）T细胞和额外的先天性白细胞上的BTLA被HVEM触发，并将负信号传递到BTLA（+）细胞中，从而干扰对这种肠道寄生虫的保护性免疫反应。
Helminths exploit intrinsic regulatory pathways of the mammalian immune system to dampen the immune response directed against them. In this article, we show that infection with the parasitic nematode Strongyloides ratti induced upregulation of the coinhibitory receptor B and T lymphocyte attenuator (BTLA) predominantly on CD4(+) T cells but also on a small fraction of innate leukocytes. Deficiency of either BTLA or its ligand herpes virus entry mediator (HVEM) resulted in reduced numbers of parasitic adults in the small intestine and reduced larval output throughout infection. Reduced parasite burden in BTLA- and HVEM-deficient mice was accompanied by accelerated degranulation of mucosal mast cells and increased Ag-specific production of the mast cell-activating cytokine IL-9. Our combined results support a model whereby BTLA on CD4(+) T cells and additional innate leukocytes is triggered by HVEM and delivers negative signals into BTLA(+) cells, thereby interfering with the protective immune response to this intestinal parasite.