HIV infection associated oxidation of innate immune proteins in the human lung mucosa alters the host response to Mycobacterium tuberculosis infection

Abstract

Abstract Tuberculosis (TB) is the leading killer of people with HIV infection. Limited studies have considered HIV infection associated changes to the soluble components of the innate immune system in the alveolar lining fluid (ALF) as a contributing factor to increased susceptibility to pulmonary infections. We hypothesize that altered function of soluble innate immune components in human ALF of HIV infected subjects, drives susceptibility to primary M.tb infection. Here, we analyzed levels and functions of various soluble innate immune molecules present in human ALF from both healthy and HIV infected subjects. We also examined the effects of ALF components from HIV positive subjects on M.tb infection of human macrophages in vitro. Our results indicate an increased oxidation of innate proteins within ALF from HIV positive subjects not treated with anti-retroviral therapy (ART). We also found that complement components and some Th1 and Th2 cytokines/chemokines significantly differed between ALF from HIV positive and healthy subjects. Moreover, we found a deficiency of binding of surfactant protein-D to M.tb in ALF from HIV positive subjects, suggesting a defective innate immune function in the lung with HIV infection. Macrophages infected with M.tb exposed to ALF from HIV positive subjects without ART were less capable of controlling the infection. Our studies provide new information on how HIV infection could modify lung mucosal innate immune responses, thereby impacting M.tb infection and potentially other pulmonary diseases in the HIV infected population without ART treatment. Our data suggest that M.tb may benefit from the declining host innate defense function of the lung mucosa during HIV infection.