Proinflammatory cytokines and type I interferon are differentially induced by virulent and avirulent mycobacteria in human macrophages (37.36)

Abstract

Abstract One third of the world's population is latently infected with Mycobacterium tuberculosis (MTB), a virulent intracellular pathogen that can survive in macrophages even in the presence of a strong adaptive immune response. The molecular mechanisms underlying MTB persistence are not fully understood. Production of type I interferon (IFN) has been linked to the exacerbation of pulmonary tuberculosis (TB) in mice. However, the role of type I IFN in human TB is as yet undefined. In this study, primary macrophages derived from elutriated monocytes of healthy individuals were infected with MTB or M. bovis Bacillus Calmette-Guérin (BCG), an attenuated vaccine strain, and their responses analyzed by qPCR. We observed that compared to BCG, MTB infection induced markedly lower expression of the NF-kB-dependent pro-inflammatory cytokine genes IL-1 and IL-8 at all time-points examined. On the other hand, transcript levels of the type I IFN associated genes CXCL10 and IFIT1 were significantly higher in MTB infected compared to BCG-infected macrophages. These findings suggest that the differential regulation of type I IFN is a determinant of mycobacterial virulence in human macrophages and that MTB may exploit the host type I IFN pathway to subvert anti-microbial programs in these host cells. This work was supported by the Intramural Research Program of the NIAID and by the Howard Hughes Medical Institute-National Institutes of Health Research Scholars Program.