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.
Stenger
S
S
Department of Microbiology and Immunology, University of California, Los Angeles, School of Medicine 90095, USA.
Niazi
K R
KR
Modlin
R L
RL
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