Tim3 binding to galectin-9 stimulates antimicrobial immunity

被引:156
作者
Jayaraman, Pushpa [1 ]
Sada-Ovalle, Isabel [1 ]
Beladi, Sarah [1 ]
Anderson, Ana C. [2 ]
Dardalhon, Valerie [2 ]
Hotta, Chie [2 ]
Kuchroo, Vijay K. [2 ]
Behar, Samuel M. [1 ]
机构
[1] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA
基金
美国国家卫生研究院;
关键词
MYCOBACTERIUM-TUBERCULOSIS INFECTION; CD8(+) T-CELLS; INTERFERON-GAMMA; INFLAMMASOME ACTIVATION; MULTIPLE-SCLEROSIS; NITRIC-OXIDE; RESPONSES; RECEPTOR; INTERLEUKIN-1; EXPRESSION;
D O I
10.1084/jem.20100687
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
T cell immunoglobulin and mucin domain 3 (Tim3) is a negative regulatory molecule that inhibits effector T(H)1-type responses. Such inhibitory signals prevent unintended tissue inflammation, but can be detrimental if they lead to premature T cell exhaustion. Although the role of Tim3 in autoimmunity has been extensively studied, whether Tim3 regulates antimicrobial immunity has not been explored. Here, we show that Tim3 expressed on T(H)1 cells interacts with its ligand, galectin-9 (Gal9), which is expressed by Mycobacterium tuberculosis-infected macrophages to restrict intracellular bacterial growth. Tim3-Gal9 interaction leads to macrophage activation and stimulates bactericidal activity by inducing caspase-1-dependent IL-1 beta secretion. We propose that the T(H)1 cell surface molecule Tim3 has evolved to inhibit growth of intracellular pathogens via its ligand Gal9, which in turn inhibits expansion of effector T(H)1 cells to prevent further tissue inflammation.
引用
收藏
页码:2343 / 2354
页数:12
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