Cutting Edge: Caspase-1 Independent IL-1β Production Is Critical for Host Resistance to Mycobacterium tuberculosis and Does Not Require TLR Signaling In Vivo

被引:355
作者
Mayer-Barber, Katrin D. [1 ]
Barber, Daniel L. [1 ]
Shenderov, Kevin [1 ]
White, Sandra D. [1 ]
Wilson, Mark S. [2 ]
Cheever, Allen [1 ]
Kugler, David [1 ]
Hieny, Sara [1 ]
Caspar, Patricia [1 ]
Nunez, Gabriel [3 ]
Schlueter, Dirk [4 ]
Flavell, Richard A. [5 ,6 ]
Sutterwala, Fayyaz S. [7 ]
Sher, Alan [1 ]
机构
[1] NIAID, Parasit Dis Lab, Immunobiol Sect, NIH, Bethesda, MD 20892 USA
[2] NIAID, Parasit Dis Lab, Immunopathogenesis Sect, NIH, Bethesda, MD 20892 USA
[3] Univ Michigan, Dept Pathol, Sch Med, Ann Arbor, MI 48109 USA
[4] Otto von Guericke Univ, Inst Med Mikrobiol, Magdeburg, Germany
[5] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA
[6] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06520 USA
[7] Univ Iowa, Div Infect Dis, Dept Internal Med, Iowa City, IA 52242 USA
基金
美国国家卫生研究院;
关键词
ADAPTIVE IMMUNITY; INNATE IMMUNITY; INFECTION; INFLAMMASOME; MICE; INTERLEUKIN-1-BETA; RECOGNITION; RESPONSES; CYTOKINE; RECEPTOR;
D O I
10.4049/jimmunol.0904189
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
To investigate the respective contributions of TLR versus lL-1R mediated signals in MyD88 dependent control of Mycobacterium tuberculosis, we compared the outcome of M. tuberculosis infection in MyD88, TRIP MyD88, IL-1R1, and IL-1 beta-deficient mice. All four strains displayed acute mortality with highly increased pulmonary bacterial burden suggesting a major role for IL-1 beta signaling in determining the MyD88 dependent phenotype. Unexpectedly, the infected MyD88 and TRIF/MyD88-deficient mice, rather than being defective in IL-1 beta expression, displayed increased cytokine levels relative to wild-type animals. Similarly, infected mice deficient in caspase-1 and ASC, which have critical functions in inflammasome-mediated IL-1 beta maturation, showed unimpaired IL-1 beta production and importantly, were considerably less susceptible to infection than IL-1 beta deficierit mice. Together our findings reveal a major role for IL-1 beta in host resistance to M. tuberculosis and indicate that during this infection the cytokine can be generated by a mechanism that does not require TLR signaling or caspase-1. The Journal of Immunology, 2010, 184: 3326-3330.
引用
收藏
页码:3326 / 3330
页数:5
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