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Slam haplotypes modulate the response to lipopolysaccharide in vivo through control of NKT cell number and function
- Source :
- Journal of immunology (Baltimore, Md. : 1950). 185(1)
- Publication Year :
- 2010
-
Abstract
- 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 α-galactosylceramide, and in NKT cell IFN-γ 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.
- Subjects :
- Lipopolysaccharides
Adoptive cell transfer
medicine.medical_treatment
Immunology
chemical and pharmacologic phenomena
Bone Marrow Cells
Receptors, Cell Surface
Article
Mice
Mice, Congenic
Immune system
Signaling Lymphocytic Activation Molecule Family Member 1
Antigens, CD
Mice, Inbred NOD
medicine
Immunology and Allergy
Animals
Lymphocyte Count
Receptor
Cells, Cultured
Mice, Knockout
Innate immune system
biology
Macrophages
hemic and immune systems
Natural killer T cell
Immunity, Innate
Mice, Inbred C57BL
Cytokine
Haplotypes
Liver
CD1D
TLR4
biology.protein
Natural Killer T-Cells
Spleen
Subjects
Details
- ISSN :
- 15506606
- Volume :
- 185
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Accession number :
- edsair.doi.dedup.....f07926688de273c05acfa1745279fe57