Abstract
Monocyte and macrophage inflammation in parenchymal tissues during acute and chronic HIV and SIV infection plays a role in early anti-viral immune responses and later in restorative responses. Macrophage polarization is observed in such responses in the central nervous system (CNS) and the heart and cardiac vessels that suggest early responses are M1 type antiviral responses, and later responses favor M2 restorative responses. Macrophage polarization is unique to different tissues and is likely dictated as much by the local microenvironment as well as other inflammatory cells involved in the viral responses. Such polarization is found in HIV infected humans, and the SIV infected animal model of AIDS, and occurs even with effective anti-retroviral therapy. Therapies that directly target macrophage polarization in HIV infection have recently been implemented, as have therapies to directly block traffic and accumulation of macrophages in tissues.
Highlights
The local microenvironment influences distinct phenotypes of macrophages
We found that the magnitude of BrdU+ monocytes of simian immunodeficiency virus (SIV)-infected monkeys predicted how rapidly they would progress to AIDS and the severity of brain histopathology (macrophage accumulation and productive viral infection)) [16]
Injection of dextran dyes directly into the ventricles in the brain to label perivascular cells, we found that the majority of M2 CD163+ macrophages found in SIVE lesions terminally were present early in the brain
Summary
The local microenvironment influences distinct phenotypes of macrophages. In 2000, a M1-M2 paradigm was adopted to distinguish between classic and alternative activated macrophages, where macrophages predominately expressing the iNOS or arginase pathways were termed M1 or M2 macrophages, respectively [1]. Evidence suggests that macrophage phenotypes are not static but dynamic and tissue microenvironment-dependent and diseases play a role in the polarization of macrophages [3,4,5]. We discuss macrophage polarization with human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infection and during acute and chronic infection of the central nervous system (CNS), peripheral nervous system (PNS) and the heart. The discussion includes the biology of monocyte/ macrophage polarization with HIV and SIV infection in tissues, traffic and accumulation of monocyte/macrophages as it relates to pathology. We discuss macrophage-associated biomarkers of CNS, PNS and cardiac disease and the need for effective adjunctive therapies targeting monocytes and macrophages in HIV infection
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