Granuloma Formation and Host Defense in Chronic Mycobacterium tuberculosis Infection Requires PYCARD/ASC but Not NLRP3 or Caspase-1

被引:107
作者
TeKippe, Erin McElvania [1 ]
Allen, Irving C. [2 ]
Hulseberg, Paul D. [3 ,4 ]
Sullivan, Jonathan T. [1 ]
McCann, Jessica R. [1 ]
Sandor, Matyas [3 ,4 ]
Braunstein, Miriam [1 ]
Ting, Jenny P. -Y. [1 ,2 ]
机构
[1] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27515 USA
[2] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA
[3] Univ Wisconsin, Dept Pathol & Lab Med, Sch Med & Publ Hlth, Madison, WI USA
[4] Univ Wisconsin, Cellular & Mol Pathol Program, Sch Med & Publ Hlth, Madison, WI USA
来源
PLOS ONE | 2010年 / 5卷 / 08期
基金
美国国家卫生研究院;
关键词
PULMONARY TUBERCULOSIS; IMMUNE-RESPONSE; CELL-DEATH; INFLAMMASOME ACTIVATION; GENE FAMILY; T-CELLS; MICE; ASC; PROTEIN; INTERLEUKIN-1-BETA;
D O I
10.1371/journal.pone.0012320
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The NLR gene family mediates host immunity to various acute pathogenic stimuli, but its role in chronic infection is not known. This paper addressed the role of NLRP3 (NALP3), its adaptor protein PYCARD (ASC), and caspase-1 during infection with Mycobacterium tuberculosis (Mtb). Mtb infection of macrophages in culture induced IL-1 beta secretion, and this requires the inflammasome components PYCARD, caspase-1, and NLRP3. However, in vivo Mtb aerosol infection of Nlrp3(-/-), Casp-1(-/-), and WT mice showed no differences in pulmonary IL-1b production, bacterial burden, or long-term survival. In contrast, a significant role was observed for Pycard in host protection during chronic Mtb infection, as shown by an abrupt decrease in survival of Pycard(-/-) mice. Decreased survival of Pycard(-/-) animals was associated with defective granuloma formation. These data demonstrate that PYCARD exerts a novel inflammasome-independent role during chronic Mtb infection by containing the bacteria in granulomas.
引用
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页数:10
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