Down-regulation of CD1 on antigen-presenting cells by infection with Mycobacterium tuberculosis.
Intracellular pathogens have developed efficient evasion strategies to survive the defenses of the host immune system. In this study, we describe a new escape mechanism utilized by Mycobacterium tuberculosis that involves the down-regulation of the Ag-presenting molecule CD1 from the cell surface of CD1+ APCs. The loss of CD1 from the cell surface is associated with a complete inhibition of the ability of the infected cells to present Ag to CD1-restricted T cells. The down-regulation of Ag-presenting molecules on CD1+ APC by infection with M. tuberculosis is unique for CD1, since the expression of the classical Ag-presenting molecules MHC class I and MHC class II is not influenced. Our data show that efficient down-regulation of CD1 requires infection of the cells with live mycobacteria, since heat killing of the bacteria completely abrogates the effect. The observed down-regulation is not due to the secretion of cytokines or other host- or pathogen-derived factors. Investigation of upstream events responsible for the down-regulation of CD1 revealed that infection with live M. tuberculosis decreased the steady state CD1-mRNA levels. This study introduces a novel evasion mechanism of M. tuberculosis that could contribute to persistence of intracellular infection by avoiding immune recognition.
Department of Microbiology and Immunology, University of California, Los Angeles, School of Medicine 90095, USA.
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Stenger
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Niazi
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Modlin
D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology*; D018949:Antigens, CD1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000502:physiology; D015850:Interleukin-6 / Q000502:physiology; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D012995:Solubility
D018949:Antigens, CD1; D015850:Interleukin-6; D012333:RNA, Messenger; D016753:Interleukin-10