Influenza virus activates inflammasomes via its intracellular M2 ion channel (Nat Immunol, 2010, 11:404-410)

報告日期: 2011/03/15
報告時間: 15:10/16:00
報告學生: 呂佳馨 (英文報告)
講評老師: 凌 斌

Full text:

Influenza virus activates inflammasomes via its intracellular M2 ion channel
 Ichinohe et al. Nature immunology 11, 404-410, 2010
Speaker: Chia-Hsing Leu (呂佳馨)
Commomtator: Dr. P. Lin(凌斌老師)
Time: 15:10~16:00, Mar. 15, 2011
Room: 602
   Influenza virus is the most pandemic infectious disease in the world. In general, influenza virus infection causes bronchitis, pneumonia, and even severe lethal pneumonia. The NLR family, pyrin domain-containing 3 (NLRP3inflammasomeis a large multiprotein complex which regulates host innate immunity to pathogenic stimulation. Influenza virus infection could activate the NLRP3 inflammasome complex in dendritic cells and macrophages. NLRP3 inflammasome mediates cytokine release by two signals: signal 1 is induced by Toll-like receptor (TLR) and activates the synthesis of pro-IL-1β, pro-IL-18, and pro-IL-33. The signal 2 istriggered by membrane perturbation, specifically potassium efflux from the cytosol increases the cleavage of pro-IL-1β, pro-IL-18, and pro-IL-33. However, the mechanism of influenza virus to activate inflammasome is still unknown. In this study, the authors find that several subtypes of influenza viruses trigger inflammasome activity through TLR7 whereas viral RNA only can not induce this effect efficiently. In addition, they use M2 mutant influenza virus and lentivirus expressing M2 to prove the M2 protein, an acid-activated ion channel, is needed for sufficiently triggering inflammasome activation in macrophage and dendritic cells. Their results show that influenza virus induces inflammasome by M2 channel which localizes in acidified trans-Golgi apparatus and depends on the pH gradient. They identify the cellular mechanism by which influenza virus infection elicits NLRP3 inflammasome. Furthermore, the authors suggest that microbial ion channels in the innate-receptors activation improve the design of effective treatments for infectious disease.
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