Slam Haplotypes Modulate the Response to Lipopolysaccharide In Vivo through Control of NKT Cell Number and Function

被引:15
作者
Aktan, Idil [1 ,2 ]
Chant, Alan [1 ,2 ]
Borg, Zachary D. [1 ,2 ]
Damby, David E. [1 ,2 ]
Leenstra, Paige C. [1 ,2 ]
Lilley, Graham W. G. [1 ,2 ]
Petty, Joseph [3 ]
Suratt, Benjamin T. [3 ]
Teuscher, Cory [2 ,3 ,4 ]
Wakeland, Edward K. [5 ]
Poynter, Matthew E. [3 ]
Boyson, Jonathan E. [1 ,2 ]
机构
[1] Univ Vermont, Coll Med, Dept Surg, Burlington, VT 05405 USA
[2] Univ Vermont, Coll Med, Vermont Ctr Immunobiol & Infect Dis, Burlington, VT 05405 USA
[3] Univ Vermont, Coll Med, Dept Med, Burlington, VT 05405 USA
[4] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA
[5] Univ Texas SW Med Ctr Dallas, Dept Immunol, Dallas, TX 75390 USA
基金
美国国家卫生研究院;
关键词
INNATE IMMUNE-RESPONSE; CONTROLS T-CELL; DENDRITIC CELLS; CUTTING EDGE; IFN-GAMMA; PSEUDOMONAS-AERUGINOSA; GLYCOLIPID ANTIGENS; GENETIC-CONTROL; ACTIVATION; MICE;
D O I
10.4049/jimmunol.0902658
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
CD1d-restricted NKT cells make up an innate-like T cell subset that plays a role in amplifying the response of innate immune leukocytes to TLR ligands. The Slam locus contains genes that have been implicated in innate and adaptive immune responses. In this study, we demonstrate that divergent Slam locus haplotypes modulate the response of macrophages to the TLR4 ligand LPS through their control of NKT cell number and function. In response to LPS challenge in vivo, macrophage TNF production in Slam haplotype-2(+) 129S1/SvImJ and 129X1/SvJ mice was significantly impaired in comparison with macrophage TNF production in Slam haplotype-1(+) C57BL/6J mice. Although no cell-intrinsic differences in macrophage responses to LPS were observed between strains, 129 mice were found to be deficient in liver NKT cell number, in NKT cell cytokine production in response to the CD1d ligand a-galactosylceramide, and in NKT cell IFN-gamma production after LPS challenge in vivo. Using B6.129c1 congenic mice and adoptive transfer, we found that divergent Slam haplotypes controlled the response to LPS in vivo, as well as the diminished NKT cell number and function, and that these phenotypes were associated with differential expression of signaling lymphocytic activation molecule family receptors on NKT cells. These data suggest that the polymorphisms that distinguish two Slam haplotypes significantly modulate the innate immune response in vivo through their effect on NKT cells. The Journal of Immunology, 2010, 185: 144-156.
引用
收藏
页码:144 / 156
页数:13
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