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 des cribe a new escape mechanism utilized by Mycobacterium tuberculosis th at involves the down-regulation of the Ag-presenting molecule CD1 from the cell surface of CD1(+) APCs. The loss of CD1 from the cell surfac e is associated with a complete inhibition of the ability of the infec ted cells to present Ag to CD1-restricted T cells. The down-regulation of Ag-presenting molecules on CD1(+) APC by infection with M. tubercu losis is unique for CD1, since the expression of the classical Ag-pres enting molecules MHC class I and MHC class II is not influenced. Our d ata show that efficient down-regulation of CD1 requires infection of t he cells with live mycobacteria, since heat killing of the bacteria co mpletely abrogates the effect. The observed down-regulation is not due to the secretion of cytokines or other host- or pathogen-derived fact ors. Investigation of upstream events responsible for the down-regulat ion of CD1 revealed that infection with live M. tuberculosis decreased the steady state CD1-mRNA levels. This study introduces a novel evasi on mechanism of M. tuberculosis that could contribute to persistence o f intracellular infection by avoiding immune recognition.