Nucleotide-binding oligomerization domain containing-like receptor family, caspase recruitment domain (CARD) containing 4 (NLRC4) regulates intrapulmonary replication of aerosolized Legionella pneumophila.
Nucleotide-binding oligomerization domain containing-like receptor family, caspase recruitment domain (CARD) containing 4 (NLRC4) regulates intrapulmonary replication of aerosolized Legionella pneumophila.
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DOI：
10.1186/1471-2334-13-371
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发表时间：
2013-08-10
影响因子：
3.7
通讯作者：
Hawn TR
中科院分区：
文献类型：
--
作者：
Berrington WR;Smith KD;Skerrett SJ;Hawn TR
嗜肺军团菌（Lp）鞭毛蛋白激活鼠巨噬细胞中控制Lp复制的信号通路。含核苷酸结合寡聚化结构域（NOD）的类受体（NLR）家族、含胱天蛋白酶募集结构域（CARD）的4（NLRC 4）和Toll样受体（TLR 5）在体外均识别Lp鞭毛蛋白，但这两种受体在体内是否发挥冗余或独立的功能作用尚不清楚。在用雾化的Lp体内感染后，分析了Nlrc 4 −/−、Nlrc 4 −/−/Tlr 5 −/−和野生型C57 Bl/6小鼠的免疫应答。与野生型对照组相比，Nlrc 4 −/−小鼠的肺部Lp清除延迟了7天。Nlrc 4 −/−/Tlr 5 −/−小鼠没有额外的缺陷。与TLR 5相反，NLRC 4不调节中性粒细胞向肺的募集。尽管在4小时时小鼠品系之间在肺转录组中没有差异，但与WT相比，Nlrc 4 −/−和Nlrc 4 −/− Tlr 5 −/−小鼠在72小时时的肺部炎症增加。与野生型（WT）和Nlrc 4 −/−小鼠相比，Nlrc 4 −/−/Tlr 5 −/−小鼠在感染后4小时和24小时的细胞因子产生也发生了变化。小鼠肺泡巨噬细胞中的Lp复制是NLRC 4依赖性和TLR 5非依赖性的。这些研究揭示了NLRC 4和TLR 5在雾化感染模型中介导对Lp鞭毛蛋白的炎症反应中的不同作用，并且NLRC 4调节肺和肺泡巨噬细胞中的复制。
Legionella pneumophila (Lp) flagellin activates signaling pathways in murine macrophages that control Lp replication. Nucleotide-binding oligomerization domain (NOD) containing-like receptor (NLR) family, caspase recruitment domain (CARD) containing 4 (NLRC4) and Toll-like Receptor (TLR5) both recognize Lp flagellin in vitro, but whether these two receptors play redundant or separate functional roles in vivo is unknown. The immune response of Nlrc4−/−, Nlrc4−/−/Tlr5−/−, and wild type C57Bl/6 mice was analyzed after in vivo infection with aerosolized Lp. Lp clearance from the lungs was delayed in Nlrc4−/− mice over seven days in comparison to wild type controls. Nlrc4−/−/Tlr5−/− mice had no additional defect. In contrast to TLR5, NLRC4 did not regulate recruitment of neutrophils to the lung. Although there were no differences among the mouse strains in the lung transcriptome at 4 hours, Nlrc4−/− and Nlrc4−/−Tlr5−/− mice had increased lung inflammation at 72 hours in comparison to WT. Nlrc4−/−/Tlr5−/− mice also had altered cytokine production at both 4 and 24 hours post infection when compared to wild-type (WT) and Nlrc4−/− mice. Lp replication in murine alveolar macrophages was NLRC4-dependent and TLR5-independent. These studies reveal that NLRC4 and TLR5 mediate different roles in the inflammatory response to Lp flagellin in an aerosolized infection model and NLRC4 regulates replication in both lungs and alveolar macrophages.
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影响因子：
5.4
作者：
Berrington, William R.;Iyer, Ravi;Wells, Richard D.;Smith, Kelly D.;Skerrett, Shawn J.;Hawn, Thomas R.
通讯作者：
Hawn, Thomas R.
影响因子：
4.4
作者：
Li, Hanfen;Willingham, Stephen B.;Ting, Jenny P. -Y.;Re, Fabio
通讯作者：
Re, Fabio
影响因子：
3.4
作者：
Archer KA;Alexopoulou L;Flavell RA;Roy CR
通讯作者：
Roy CR
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
32.4
作者：
Khare S;Dorfleutner A;Bryan NB;Yun C;Radian AD;de Almeida L;Rojanasakul Y;Stehlik C
通讯作者：
Stehlik C