Innate Immune Defense Mechanisms in the Intestine

描述(申请人提供)：人体肠道微生物组包括在真核细胞、植物、真菌或细菌中复制的病毒。然而，人们对此知之甚少。 病毒识别塑造粘膜免疫反应。此外，对感应病毒以诱导I型干扰素的信号中间体的详细了解对于抑制阻碍天然免疫防御的病毒机制的策略至关重要。我们的工作确定了由arhgef2基因编码的鸟嘌呤核苷酸交换因子h1(gef-h1)是病毒感染过程中宿主防御激活的中心成分。我们假设，全球环境基金-H1通过控制干扰素反应因子的激活来作为天然宿主防御的守门人，干扰素反应因子是识别细菌和病毒所诱导的信号通路的一部分。确定这个新发现的微生物模式识别中心组件的功能作用应该会为抗病毒宿主防御的整合提供关键的见解 进入控制肠道微生物区系的免疫激活途径。

DESCRIPTION (provided by applicant): The human intestinal microbiome includes viruses that replicate in eukaryotic cells, plants, fungi or bacteria. However, very little is known on how viral recognition shapes mucosal immune responses. Furthermore, a detailed understanding of the signaling intermediates that confer the sensing of viruses for induction of type I interferons s critical for strategies to curtail viral mechanisms that impede innate immune defenses. Our work identified the guanine nucleotide exchange factor H1 (GEF-H1), encoded by the arhgef2 gene, as a central component of host defense activation during viral infections. We hypothesize that GEF-H1 serves as a gatekeeper for innate host defenses by controlling interferon response factor activation, which is part of signaling pathways induced by recognition of bacteria and viruses. Defining the functional role of this newly discovered central component of microbial pattern recognition should provide pivotal insights into the integration of antiviral host defenses into immune activation pathways that control the microbiota in the intestine.