Down-regulation of CD1 on antigen-presenting cells by infection with Mycobacterium tuberculosis

S Stenger, KR Niazi, RL Modlin - The Journal of Immunology, 1998 - journals.aai.org
S Stenger, KR Niazi, RL Modlin
The Journal of Immunology, 1998journals.aai.org
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 …
Abstract
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.
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