Suppression of IFN-gamma-induced chemokines from bronchial epithelial cells bymycobacterium tuberculosis

Abstract

Rational: Pulmonary Mycobacterium tuberculosis (MTB) infection remains a major public health problem in most part of the world. Molecular mechanisms of the pathogenesis of MTB are still incompletely understood. Innate immune responses of bronchial epithelial cells are now known to play a pivotal role when encountering with inhaled pathogens. To elucidate the impact of MTB on human bronchial epithelial cells, we tested the hypothesis that MTB can modulate the response of epithelium to favor persistence of MTB infection. Methods: A bronchial epithelial cell line (BEAS-2B) was stimulated with IFN-gamma and tuberculin, an extract derived from MTB. Cell extracts were collected to measure mRNA (RT-PCR) and supernatants were collected to measure protein (ELISA) after 6 hours of stimulation. MTB extract was fractionated by filtration based on molecular weight or heated for initial characterization of active compounds within the extract. Results: MTB extract induced both CXCL8 mRNA and protein. Whereas, MTB extract profoundly suppressed IFN-gamma-induced CXCL10 in a dose dependent manner. Low molecular weight MTB extract (LMW; below 50 kDa) retained the suppressive effect, but high molecular weight (HMW; above 50 kDa) was modest. Heated MTB extract still possessed suppressive effect of IFN-gamma-induced CXCL10. Conclusions: Exposure of bronchial epithelial cells to MTB extracts may suppress IFN signaling and leading to incomplete immune response to MTB infection.