HIV and the tuberculosis "set point": how HIV impairs alveolar macrophage responses to tuberculosis and sets the stage for progressive disease

• Type of Material: Article
• Authors: Sara Auld, Emory University; Bashar Staitieh, Emory University
• Language: English
• Date: 2020-09-23
• Publisher: BMC
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2020
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s12977-020-00540-2
• Title of Journal or Parent Work: RETROVIROLOGY
• Volume: 17
• Issue: 1
• Start Page: 32
• End Page: 32
• Grant/Funding Information: This work was supported by the following grants: NIH/NIAID K23 AI134182 (Auld), NIH/NIAAA K08 AA024512 (Staitieh), the Emory Center for AIDS Research (P30AI050409).
• Keywords: HIV; MYCOBACTERIUM-TUBERCULOSIS; IMMUNE-RESPONSES; Life Sciences & Biomedicine; Science & Technology; Macrophages; Tuberculosis; HUMAN-IMMUNODEFICIENCY-VIRUS; Coinfection; UNDERLYING MECHANISMS; Virology; T-CELLS; POSITRON-EMISSION; PULMONARY TUBERCULOSIS; GLUTATHIONE LEVELS; INFECTION; POLARIZATION; Innate immunity
• Research Categories: Health Sciences, Immunology; Biology, Virology; Biology, Cell

Abstract

As HIV has fueled a global resurgence of tuberculosis over the last several decades, there is a growing awareness that HIV-mediated impairments in both innate and adaptive immunity contribute to the heightened risk of tuberculosis in people with HIV. Since early immune responses to Mycobacterium tuberculosis (Mtb) set the stage for subsequent control or progression to active tuberculosis disease, early host-pathogen interactions following Mtb infection can be thought of as establishing a mycobacterial "set point,"which we define as the mycobacterial burden at the point of adaptive immune activation. This early immune response is impaired in the context of HIV coinfection, allowing for a higher mycobacterial set point and greater likelihood of progression to active disease with greater bacterial burden. Alveolar macrophages, as the first cells to encounter Mtb in the lungs, play a critical role in containing Mtb growth and establishing the mycobacterial set point. However, a number of key macrophage functions, ranging from pathogen recognition and uptake to phagocytosis and microbial killing, are blunted in HIV coinfection. To date, research evaluating the effects of HIV on the alveolar macrophage response to Mtb has been relatively limited, particularly with regard to the critical early events that help to dictate the mycobacterial set point. A greater understanding of alveolar macrophage functions impacted by HIV coinfection will improve our understanding of protective immunity to Mtb and may reveal novel pathways amenable to intervention to improve both early immune control of Mtb and clinical outcomes for the millions of people worldwide infected with HIV.