Cell-cell propagation of NF-kB transcription factor and MAP kinase activation amplifies innate immunity against bacterial infection (Immunity, 2010, 33:804-816)

報告日期: 2011/03/08
報告時間: 16:00/16:50
報告學生: 蔡宗婷 (英文報告)
講評老師: 林以行
附件下載:

Full text: http://basicmed.med.ncku.edu.tw/admin/up_img/000308-2.pdf

Cell-cell propagation of NF-kB transcription
factor and MAP kinase activation amplifies
innate immunity against bacterial Infection
 
Kasper CA, Sorg I, Schmutz C, Tschon T, Wischnewski H, Kim ML, Arrieumerlou C. (2010).Immunity. 24, 804-16.
 
Speaker: 蔡宗婷
Commentator: 林以行老師
Time:2011/03/08 16:00-16:50
Place:Room 602
 
Abstract
 
  Gut epithelial cells play the key role in the host defense against microbial infection. Shigella flexneri is a Gram negative foodborne bacterium that invades gut epithelium cells in humans, causing an acute mucosal inflammation called Shigellosis or bacillary dysentery. Interestingly, despite the S. flexneri uses multiple secreted effector proteins to interfere interleukin-8 (IL-8) expression in infected epithelial
cells, massive IL-8 secretion is still observed during Shigellosis. Thus, the authors suggest that there is a host mechanism that can compensate for bacterial effect. In this study, by monitoring proinflammatory signals at the single-cell level, they found the NF-kB and MAP kinase, JNK, ERK, and p38 were rapidly propagated from infected cells to uninfected nearby cells, leading to IL-8 production by uninfected bystander cells. And this IL-8 bystander-effect can also be found during Listeria monocytogenes and Salmonella typhimurium infection. Besides, the host factor, the pattern recognition receptor NOD1 sensing was found to participate in the bystander-effect by using the NOD1 ligand microinjection. This bystander activation was not induced via the receptor mediated paracrine signaling, but was cell-cell contact dependent. Instead, the IL-8 expression in bystander cells was strongly reduced when gap junction inhibitor 18β-glycyrrhetinic acid was used. Yet, the NF-kB, JNK, p38, and ERK activation and IL-8 expression were increased when overexpressing the gap junction molecule conexin43 on A431 cells. This result indicated that the cell-cell propagation of inflammatory signals was mediated by gap junctions. It provides an important new way to explain how the innate immune responses can be amplified at the early stages of bacterial infection.
 
References
1.         Hardt WD. (2010). Infected cell in trouble: bystander cells ring the bell. Immunity. 24, 804-16.
2.         Dolowschiak T, Chassin C, Ben Mkaddem S, Fuchs TM, Weiss S, Vandewalle A, Hornef MW. (2011). Potentiation of epithelial innate host responses by intercellular communication. PLoS Pathog. 18, e1001194.