The macrophage in HIV-1 infection: from activation to deactivation?
Macrophages play a crucial role in innate and adaptative immunity in response to microorganisms and are an important cellular target during HIV-1 infection. Recently, the heterogeneity of the macrophage population has been highlighted. Classically activated or type 1 macrophages (M1) induced in particular by IFN-gamma display a pro-inflammatory profile. The alternatively activated or type 2 macrophages (M2) induced by Th-2 cytokines, such as IL-4 and IL-13 express anti-inflammatory and tissue repair properties. Finally IL-10 has been described as the prototypic cytokine involved in the deactivation of macrophages (dM). Since the capacity of macrophages to support productive HIV-1 infection is known to be modulated by cytokines, this review shows how modulation of macrophage activation by cytokines impacts the capacity to support productive HIV-1 infection. Based on the activation status of macrophages we propose a model starting with M1 classically activated macrophages with accelerated formation of viral reservoirs in a context of Th1 and proinflammatory cytokines. Then IL-4/IL-13 alternatively activated M2 macrophages will enter into the game that will stop the expansion of the HIV-1 reservoir. Finally IL-10 deactivation of macrophages will lead to immune failure observed at the very late stages of the HIV-1 disease.
Herbein
Georges
G
Department of Virology, UPRES EA 4266 Pathogens and Inflammation, IFR 133 INSERM, Franche-Comte University, CHU Besançon, Besançon, France. georges.herbein@univ-fcomte.fr
Varin
Audrey
A
D016207:Cytokines / Q000276:immunology; D015497:HIV-1 / Q000276:immunology* / Q000472:pathogenicity*; D006801:Humans; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology* / Q000821:virology*; D008954:Models, Biological; D014779:Virus Replication
D016207:Cytokines