Macrophages and HIV/AIDS Pathogenesis: Lessons from the Rhesus Macaque Model

Abstract

Destruction of CD4+ T cells is a primary cause of immunodeficiency in Human Immunodeficiency Virus (HIV)-infected humans and Simian Immunodeficiency Virus (SIV)-infected rhesus macaques. Tissue macrophages, however, also contribute to AIDS pathogenesis. Studies on rhesus macaque lung revealed the presence of at least two types of macrophages comprising short-lived lung interstitial macrophages in the parenchyma that are not present in bronchoalveolar lavage (BAL), and the long-lived alveolar macrophages that predominate in BAL and rarely divide. Increased blood monocyte turnover was associated with death of infected short-lived tissue macrophages and terminal disease progression during AIDS. Antiretroviral therapy (ART) treatment of SIV-infected macaques effectively prevented active infection of short-lived macrophages in tissues and delayed disease progression. Interestingly however, longer-lived macrophages remained infected and survived despite ART. This suggests that the long-lived macrophages contribute to establishing a virus reservoir and that these infected persistent cells likely become dysregulated to promote chronic inflammation. Furthermore, macrophages are the predominant immunological cells in heart, adipose tissue, and lung, and these were primarily of the long-lived macrophage subset. Information about macrophages garnered from the SIV rhesus macaque model provides a basis to further develop intervention strategies that target macrophages for reducing chronic inflammatory co-morbidities and remove a contributing viral reservoir for achieving cure.