Role of macrophages in the immunopathogenesis of HIV-1 infection

Abstract

Macrophages have important functions in both alerting and activating the immune system. They have the ability to activate both the innate and adaptive immune responses through their role as antigen presenting cells, presenting viral antigens to immune cells. They can further reduce the viral burden by removing dead and dying cells, and they themselves contain several restriction factors that offer a level of protection against HIV-1 infection. However, macrophages also have a central role in the pathogenesis of HIV-1 infection. Through the secretion of chemokines, they can recruit T cells to the site of infection and provide new cellular targets for HIV-1. They have the ability to harbor HIV-1 in their internal vesicles, and facilitate infection of cells through cell,–cell transfer of HIV-1. In addition, macrophages have a long-life span, and through persistent infection and recruitment of cellular targets, they can contribute to the viral reservoir. A viral reservoir is a cell or anatomical site where replication-competent HIV-1 accumulates and persists stably. Additionally macrophages, reside in multiple tissues within the body, including the central nervous system, creating complications for immune detection and penetration of current antiretroviral therapies. The multi faceted role of macrophages during HIV-1 disease pathogenesis makes them important immune cells to be considered in future HIV-1 elimination strategies.