Microbial Degradation of Cellular Kinases Impairs Innate Immune Signaling and Paracrine TNFα Responses.
Microbial Degradation of Cellular Kinases Impairs Innate Immune Signaling and Paracrine TNFα Responses.
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DOI：
10.1038/srep34656
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发表时间：
2016-10-04
影响因子：
4.6
通讯作者：
Genco CA
中科院分区：
文献类型：
--
作者：
Barth K;Genco CA
The NFκB and MAPK signaling pathways are critical components of innate immunity that orchestrate appropriate immune responses to control and eradicate pathogens. Their activation results in the induction of proinflammatory mediators, such as TNFα a potent bioactive molecule commonly secreted by recruited inflammatory cells, allowing for paracrine signaling at the site of an infection. In this study we identified a novel mechanism by which the opportunistic pathogen Porphyromonas gingivalis dampens innate immune responses by disruption of kinase signaling and degradation of inflammatory mediators. The intracellular immune kinases RIPK1, TAK1, and AKT were selectively degraded by the P. gingivalis lysine-specific gingipain (Kgp) in human endothelial cells, which correlated with dysregulated innate immune signaling. Kgp was also observed to attenuate endothelial responsiveness to TNFα, resulting in a reduction in signal flux through AKT, ERK and NFκB pathways, as well as a decrease in downstream proinflammatory mRNA induction of cytokines, chemokines and adhesion molecules. A deficiency in Kgp activity negated decreases to host cell kinase protein levels and responsiveness to TNFα. Given the essential role of kinase signaling in immune responses, these findings highlight a unique mechanism of pathogen-induced immune dysregulation through inhibition of cell activation, paracrine signaling, and dampened cellular proinflammatory responses.
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影响因子：
3.7
作者：
Balwani S;Chaudhuri R;Nandi D;Jaisankar P;Agrawal A;Ghosh B
通讯作者：
Ghosh B
影响因子：
7.7
作者：
Devin, A;Lin, Y;Liu, ZG
通讯作者：
Liu, ZG
DOI：
10.1186/1478-811x-11-84
发表时间：
2013-11-07
期刊：
Cell communication and signaling : CCS
影响因子：
--
作者：
Hayashi K;Piras V;Tabata S;Tomita M;Selvarajoo K
通讯作者：
Selvarajoo K
影响因子：
4.4
作者：
Amar, Salomon;Wu, Shou-chieh;Madan, Monika
通讯作者：
Madan, Monika
影响因子：
30.5
作者：
Arbibe, Laurence;Kim, Dong Wook;Sansonetti, Philippe J.
通讯作者：
Sansonetti, Philippe J.