Inhibition of cell surface MHC class II expression by Salmonella

被引:52
作者
Mitchell, EK
Mastroeni, P
Kelly, AP
Trowsdale, J
机构
[1] Univ Cambridge, Dept Pathol, Div Immunol, Cambridge CB2 1QP, England
[2] Univ Cambridge, Dept Clin Vet Med, Ctr Vet Sci, Bacterial Infect Grp, Cambridge CB2 1QP, England
基金
英国医学研究理事会;
关键词
bacterial; human; antigen presentation; MHC;
D O I
10.1002/eji.200425314
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Peptide presentation by MHC molecules is an essential component of the adaptive immune response. To persist in a host, many pathogens have evolved strategies that interfere with MHC antigen-presentation. We show that in human cells harboring intracellular Salmonella, MHC class II cell surface expression was substantially reduced. The effect was specific for MHC class II as expression of additional surface receptors remained unchanged. We investigated the underlying mechanism and showed that class II biosynthesis and peptide loading were unaffected by the presence of Salmonella; however, infection led to an intracellular accumulation of mature molecules. The intracellular class II colocalized with lysosome-associated membrane protein-1 and HLA-DM but not with the Salmonella-containing vacuole. Using Salmonella mutants defective in different components and effectors of the Salmonella pathogenicity island-2 type-III secretion system, we traced the effect on class II to the sifA locus. SifA has been shown to be involved in recruiting membrane for the Salmonella-containing vacuoles. Our data suggest an additional role for SifA in interfering with MHC class II antigen-presentation.
引用
收藏
页码:2559 / 2567
页数:9
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