Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome (Nat Immunol, 2011, doi:10.1038/ni.1980)

報告日期: 2011/03/29
報告時間: 17:10/18:00
報告學生: 陳盈達
講評老師: 蕭璦莉
附件下載:

Full text: http://basicmed.med.ncku.edu.tw/admin/up_img/000329-3.pdf

Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome
 
Nakahira, K. et al. Nat. Immunol. 2011, 12: 222-30
 
Speaker: Ying-Da Chen (陳盈達)
Commentator: Chih-Peng Chang,Ph.D.(張志鵬博士)
Time: 17:10~18:00, March 29, 2011
Place: Room 602
 
Abstract:
 
Autophagy is a cellular process responsible to degrade damaged proteins and old organelles. Furthermore, autophagy also plays an important role in the clearance of intracellular pathogens and regulates cytokine secretion in the immune response (1). Loss of the autophagic proteins may decrease the secretion of IL-1β and IL-18, however, the mechanisms remain unclear (2). Inflammasome is a multiprotein complex including NALP family proteins. Previous study showed that in macrophages, the secretion of IL-1β and IL-18 are mediated by inflammasome.In this study, the authors proved that deletion of the autophagic proteins LC3B and beclin 1 of macrophageswould increasecaspase-1 activity and the secretion of IL-1β and IL-18. Moreover, abnormal mitochondria and translocation of mitochondrial DNA were observed in lipopolysaccharide (LPS) and ATP treatment.NALP3 inflammasome and mitochondrial reactive oxygen species were required for release of mitochondrial DNA into the cytosol.In vivo study showed that mice with LC3B deficiency produced more IL-1β and IL-18 in sepsis models which were susceptible to LPS treatment. This study suggests that autophagic proteins may regulate the NALP3-dependent inflammation through maintaining the integrity of mitochondria.
 
References:
1.        Virgin, H.W. & levine, B. Autophagy genes in immunity. Nat. Immunol. 10, 461–470 (2009).
2.        Saitoh, T. Fujita, N. Jang, M.H. Uematsu, S. Yang, B.G. Satoh, T. Omori, H. Noda, T. Yamamoto, N. Komatsu, M. Tanaka, K. Kawai, T. Tsujimura, T. Takeuchi, O. Yoshimori, T. & Akira, S. Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1β production. Nature 456, 264–268 (2008).