IL-1α signaling initiates the inflammatory response to virulent Legionella pneumophila in vivo.
IL-1α signaling initiates the inflammatory response to virulent Legionella pneumophila in vivo.
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DOI：
10.4049/jimmunol.1300100
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发表时间：
2013-06-15
期刊：
影响因子：
--
通讯作者：
Vance RE
中科院分区：
文献类型：
--
作者：
Barry KC;Fontana MF;Portman JL;Dugan AS;Vance RE
嗜肺军团菌是一种细胞内细菌病原体，是导致人类严重肺炎的原因，称为军团病。L.嗜肺菌的发病机制是嗜中性粒细胞快速流入肺部，这是响应于经由白细胞介素-1受体（IL-1 R）的信号传导而发生的。两种不同的细胞因子IL-1α和IL-1β可以刺激IL-1 R。IL-1β是在被称为炎性小体的细胞溶质传感器激活后产生的，炎性小体检测L. pneumophila在体外和体内。令人惊讶的是，我们发现IL-1β在嗜中性粒细胞对L.嗜肺菌相反，我们发现白细胞介素-1 α是L.嗜肺菌感染的小鼠。我们发现，中性粒细胞募集反应毒力L。嗜肺细胞需要造血细胞特异性地产生IL-1α。与IL-1β相反，导致IL-1α产生的先天性信号通路响应于L.嗜肺菌的定义仍然不明确。特别是，虽然我们证实了炎性小体在体内启动IL-1β信号传导中的作用，但我们发现炎性小体在IL-1α的产生中没有重要作用。相反，我们提出一种新的宿主途径，可能涉及抑制宿主蛋白质的合成，是负责IL-1α的生产，响应有毒L。嗜肺菌我们的结果证实IL-1α是对L. pneumophila在体内的表达，并指出IL-1α在体内提供炎性小体介导的免疫应答的替代中的重要作用。
Legionella pneumophila is an intracellular bacterial pathogen that is the cause of a severe pneumonia in humans called Legionnaires’ Disease. A key feature of L. pneumophila pathogenesis is the rapid influx of neutrophils into the lungs, which occurs in response to signaling via the interleukin-1 receptor (IL-1R). Two distinct cytokines, IL-1α and IL-1β, can stimulate the IL-1R. IL-1β is produced upon activation of cytosolic sensors called inflammasomes that detect L. pneumophila in vitro and in vivo. Surprisingly, we find no essential role for IL-1β in neutrophil recruitment to the lungs in response to L. pneumophila. Instead, we show that interleukin-1α is a critical initiator of neutrophil recruitment to the lungs of L. pneumophila-infected mice. We find that neutrophil recruitment in response to virulent L. pneumophila requires the production of IL-1α specifically by hematopoietic cells. In contrast to IL-1β, the innate signaling pathways that lead to the production of IL-1α in response to L. pneumophila remain poorly defined. In particular, although we confirm a role for inflammasomes for initiation of IL-1β signaling in vivo, we find no essential role for inflammasomes in production of IL-1α. Instead, we propose that a novel host pathway, perhaps involving inhibition of host protein synthesis, is responsible for IL-1α production in response to virulent L. pneumophila. Our results establish IL-1α as a critical initiator of the inflammatory response to L. pneumophila in vivo, and point to an important role for IL-1α in providing an alternative to inflammasome-mediated immune responses in vivo.
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影响因子：
4.4
作者：
Bellocchio, S;Montagnoli, C;Romani, L
通讯作者：
Romani, L
影响因子：
4.4
作者：
Kafka, Daniel;Ling, Eduard;Mizrachi-Nebenzahl, Yaffa
通讯作者：
Mizrachi-Nebenzahl, Yaffa
影响因子：
3.4
作者：
Archer KA;Alexopoulou L;Flavell RA;Roy CR
通讯作者：
Roy CR
DOI：
10.4049/jimmunol.1200195
发表时间：
2012-06-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Cai S;Batra S;Wakamatsu N;Pacher P;Jeyaseelan S
通讯作者：
Jeyaseelan S
影响因子：
56.9
作者：
CERRETTI, DP;KOZLOSKY, CJ;BLACK, RA
通讯作者：
BLACK, RA