Both TRIF- and MyD88-dependent signaling contribute to host defense against pulmonary Klebsiella infection.
Both TRIF- and MyD88-dependent signaling contribute to host defense against pulmonary Klebsiella infection.
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DOI：
10.4049/jimmunol.0901033
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发表时间：
2009-11-15
期刊：
影响因子：
--
通讯作者：
Jeyaseelan S
中科院分区：
文献类型：
--
作者：
Cai S;Batra S;Shen L;Wakamatsu N;Jeyaseelan S
Klebsiella pneumoniae (Kp) causes extensive lung damage. Toll-like receptor (TLR) signaling involves adaptors TRIF and MyD88. However, the relative contribution of TRIF and MyD88 signaling in host defense against pulmonary Kp infection have not been elucidated. Therefore, we investigated the role of TRIF and MyD88 in Kp pneumonia. TRIF−/− mice infected with Kp showed impaired survival and reduced bacterial clearance, neutrophil influx, histopathologic evidence of inflammation, and TNF-α, IL-6, KC, MIP-2, but not LIX, expression in the lungs. In addition, Kp-induced late NF-κB activation and phosphorylation of MAP kinases was attenuated in the lungs of TRIF−/− mice. However, MyD88−/− mice infected with Kp showed a much more remarkable phenotype, including impaired survival and reduced bacterial clearance, histopathology, and TNF-α, IL-6, KC, MIP-2 and LIX expression with almost no neutrophil influx in the lungs. In MyD88−/− mice, Kp-induced early NF-κB and MAPK activation in the lungs was also reduced. Furthermore, the role of MyD88 is dominant over TRIF because TRIF/MyD88 double-knockout mice displayed a more pronounced phenotype than TRIF−/− mice. Moreover, human alveolar macrophages pretreated with MyD88 blocking peptide showed attenuated TNF-α, IL-6 and IL-8 expression. Also, C57Bl/6 mice pretreated with MyD88 blocking peptide (BP) exhibited attenuation in Kp-induced neutrophil influx and enhanced bacterial burden in the lungs and dissemination. Overall, this investigation provides new insights into the TRIF and MyD88 signaling triggered by pulmonary Kp infection in the lungs and demonstrate the therapeutic potential of MyD88 in reducing excessive neutrophil influx in human disease during Gram-negative bacterial pneumonia.
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DOI：
10.1165/rcmb.2008-0152oc
发表时间：
2009-06-01
影响因子：
6.4
作者：
Cai, Shanshan;Zemans, Rachel L.;Jeyaseelan, Samithamby
通讯作者：
Jeyaseelan, Samithamby
影响因子：
4.4
作者：
Jeyaseelan, Samithamby;Young, Scott K.;Worthen, G. Scott
通讯作者：
Worthen, G. Scott
影响因子：
8.8
作者：
Abraham, E
通讯作者：
Abraham, E
影响因子：
5.5
作者：
Chelvarajan, R. Lakshman;Liu, Yushu;Bondada, Subbarao
通讯作者：
Bondada, Subbarao
影响因子：
4.4
作者：
Jeyaseelan, Samithamby;Young, Scott K.;Worthen, G. Scott
通讯作者：
Worthen, G. Scott