MyD88 and Type I Interferon Receptor-Mediated Chemokine Induction and Monocyte Recruitment during Listeria monocytogenes Infection
MyD88 and Type I Interferon Receptor-Mediated Chemokine Induction and Monocyte Recruitment during Listeria monocytogenes Infection
复制标题
DOI：
10.4049/jimmunol.0900460
复制
发表时间：
2009-07-15
影响因子：
4.4
通讯作者：
Pamer, Eric G.
中科院分区：
文献类型：
--
作者：
Jia, Ting;Leiner, Ingrid;Pamer, Eric G.
单核细胞在防御感染中发挥核心作用，但促进单核细胞募集和激活的机制仍不完全明确。单核细胞增生李斯特菌是一种细胞内细菌病原体，防御需要体内MCP-1诱导和ccr2依赖性的Ly6C（高）单核细胞从骨髓募集到感染部位。本研究表明，强毒单核增生乳杆菌感染骨髓源性巨噬细胞可分两个阶段诱导MCP-1表达。第一阶段是快速的，诱导MCP-1的低水平产生，并依赖于TLR/MyD88信号。第二阶段促进长时间、高水平的MCP-1分泌，并依赖于I型IFN受体（IFNAR）的信号传导。尽管仍局限于吞噬体的减毒单核增生乳杆菌菌株触发TLR/ myd88介导的信号并诱导低水平MCP-1表达，但只有细胞质侵入细菌促进ifna依赖性MCP-1表达。在体内，MyD88或IFNAR信号的缺乏都不会损害早期单核细胞从骨髓的迁移和向感染脾脏的募集。然而，MyD88和ifnar介导的MCP-1诱导的缺失会导致Ly6C（高）单核细胞募集不足和对单核细胞增生乳杆菌感染的易感性增加。我们的研究表明，不同但部分重叠的信号转导途径提供了冗余，确保了最佳的单核细胞募集到微生物感染部位。免疫学杂志，2009,33(3):1271-1278。
Monocytes play a central role in defense against infection, but the mechanisms promoting monocyte recruitment and activation remain incompletely defined. Defense against Listeria monocytogenes, an intracellular bacterial pathogen, requires in vivo MCP-1 induction and CCR2-dependent recruitment of Ly6C(high) monocytes from bone marrow to sites of infection. Herein, we demonstrate that infection of bone marrow-derived macrophages with virulent L. monocytogenes induces MCP-1 expression in two phases. The first phase is rapid, induces low-level production of MCP-1, and is dependent on TLR/MyD88 signaling. The second phase promotes prolonged, higher level MCP-1 secretion and is dependent on signaling via the type I IFN receptor (IFNAR). Although attenuated L. monocytogenes strains that remain confined to the phagosome trigger TLR/MyD88-mediated signals and induce low-level MCP-1 expression, only cytosol-invasive bacteria promote IFNAR-dependent MCP-1 expression. In vivo, deficiency of either MyD88 or IFNAR signaling does not impair early monocyte emigration from bone marrow and recruitment to infected spleen. Loss of both MyD88 and IFNAR-mediated MCP-1 induction, however, results in deficient Ly6C(high) monocyte recruitment and increased susceptibility to L. monocytogenes infection. Our studies demonstrate that distinct but partially overlapping signal transduction pathways provide redundancy that ensures optimal monocyte recruitment to sites of microbial infection. The Journal of Immunology, 2009, 183: 1271-1278.