Multiple MyD88-dependent responses contribute to pulmonary clearance of Legionella pneumophila.
Multiple MyD88-dependent responses contribute to pulmonary clearance of Legionella pneumophila.
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DOI：
10.1111/j.1462-5822.2008.01234.x
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发表时间：
2009-01
影响因子：
3.4
通讯作者：
Roy CR
中科院分区：
文献类型：
--
作者：
Archer KA;Alexopoulou L;Flavell RA;Roy CR
myd88依赖性信号在嗜肺军团菌感染的早期炎症细胞因子分泌和宿主保护中发挥重要作用。虽然TLR2有助于MyD88依赖性的嗜肺乳杆菌清除，但MyD88的tlr非依赖性功能也可能很重要。为了确定为什么MyD88对嗜肺乳杆菌的宿主保护至关重要，研究了小鼠中多种tlr和IL-18受体（IL-18R）依赖性IFN-γ产生的贡献。缺乏TLR5或TLR9的小鼠，或缺乏TLR2和TLR5或TLR9中的任何一个的小鼠，能够控制细菌的复制，并且在细胞因子的产生方面与对照小鼠相比没有明显的缺陷。肺中myd88依赖性IFN-γ的产生主要由NK细胞介导，并需要IL-18R信号传导。降低IFN-γ水平对感染小鼠嗜肺乳杆菌的复制或清除动力学没有很大影响。此外，IFN-γ缺乏小鼠没有myd88缺乏小鼠那么严重的易感表型，并且能够控制嗜肺乳杆菌的肺部感染。因此，嗜肺乳杆菌诱导的myd88依赖性先天免疫反应既涉及tlr依赖性反应，也涉及NK细胞il - 18r依赖性IFN-γ的产生，这些myd88依赖性途径可以独立发挥作用，为宿主提供抗细胞内病原体的保护。
MyD88-dependent signaling is important for secretion of early inflammatory cytokines and host protection in response to Legionella pneumophila infection. Although TLR2 contributes to MyD88-dependent clearance of L. pneumophila, TLR-independent functions of MyD88 could also be important. To determine why MyD88 is critical for host protection to L. pneumophila the contribution of multiple TLRs and IL-18 receptor (IL-18R)-dependent IFN-γ production in a mouse. Mice deficient for TLR5 or TLR9, or deficient for TLR2 along with either TLR5 or TLR9, were competent for controlling bacterial replication and had no apparent defects in cytokine production compared to control mice. MyD88-dependent production of IFN-γ in the lung was mediated primarily by NK cells and required IL-18R signaling. Reducing IFN-γ levels did not greatly affect the kinetics of L. pneumophila replication or clearance in infected mice. Additionally, IFN-γ-deficient mice did not have a susceptibility phenotype as severe as the MyD88-deficient mice and were able to control a pulmonary infection by L. pneumophila. Thus, MyD88-dependent innate immune responses induced by L. pneumophila involve both TLR-dependent responses and IL-18R-dependent production of IFN-γ by NK cells, and these MyD88-dependent pathways can function independently to provide host protection against an intracellular pathogen.
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影响因子：
56.9
作者：
Blander, JM;Medzhitov, R
通讯作者：
Medzhitov, R
一种常见的主导TLR5停止密码子多态性废除了鞭毛蛋白信号传导，并与对军团疾病的易感性有关。
影响因子：
15.3
作者：
Hawn, TR;Verbon, A;Lettinga, KD;Zhao, LP;Li, SS;Laws, RJ;Skerrett, SJ;Beutler, B;Schroeder, L;Nachman, A;Ozinsky, A;Smith, KD;Aderem, A
通讯作者：
Aderem, A
影响因子：
3.1
作者：
Akamine, M;Higa, F;Saito, A
通讯作者：
Saito, A
影响因子：
3.1
作者：
Brieland, JK;Remick, DG;Fantone, JC
通讯作者：
Fantone, JC
DOI：
10.1073/pnas.0605200103
发表时间：
2006-08-15
影响因子：
11.1
作者：
Feuillet, Vincent;Medjane, Samir;Alexopoulou, Lena
通讯作者：
Alexopoulou, Lena