HIV Infection impairs the Host Response toMycobacterium tuberculosisInfection by altering Surfactant Protein D function in the Human Lung Alveolar Mucosa

Abstract

Tuberculosis is the leading cause of death for people living with HIV (PLWH). We hypothesized that altered functions of innate immune components in the human alveolar lining fluid of PLWH (HIV-ALF), drive susceptibility toMycobacterium tuberculosis(M.tb) infection. Our results indicate a significant increase in oxidation of innate proteins and chemokine levels, and significantly lower levels and function of complement components and Th1/Th2/Th17 cytokines in HIV-ALFvs.control-ALF (non-HIV infected people). We further found a deficiency of surfactant protein-D (SP-D) and reduced binding of SP-D toM.tbthat had been exposed to HIV-ALF. Primary human macrophages infected withM.tbexposed to HIV-ALF were significantly less capable of controlling the infection, which was reversed by SP-D replenishment in HIV-ALF. Thus, our data suggest that PLWH without antiretroviral therapy (ART) have declining host innate defense function in their lung mucosa, thereby favoringM.tband potentially other pulmonary infections.

Impact of the elderly lung mucosa onMycobacterium tuberculosismetabolic adaptation during infection of alveolar epithelial cells

“…Human BALF from healthy young and elderly donors was concentrated to obtain ALF at its physiological concentration within the human lung (1 mg/mL of phospholipid) as we reported in detail (10, 13–15, 24, 81).…”