Department of Virology, UPRES EA 4266 Pathogens and Inflammation, IFR 133 INSERM, Franche-Comte University, CHU Besançon, Besançon, France.
Retrovirology. 2010 Apr 9;7:33. doi: 10.1186/1742-4690-7-33.
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.
巨噬细胞在应对微生物的先天和适应性免疫中发挥着至关重要的作用，并且是 HIV-1 感染过程中的重要细胞靶标。最近，巨噬细胞群体的异质性已得到强调。经典激活或 1 型巨噬细胞（M1），特别是由 IFN-γ诱导，表现出促炎特征。由 Th2 细胞因子（如 IL-4 和 IL-13）诱导的替代激活或 2 型巨噬细胞（M2）表达抗炎和组织修复特性。最后，IL-10 被描述为参与巨噬细胞失活（dM）的典型细胞因子。由于巨噬细胞支持 HIV-1 感染的能力已知受到细胞因子的调节，因此本综述展示了细胞因子如何调节巨噬细胞的激活，从而影响支持 HIV-1 感染的能力。基于巨噬细胞的激活状态，我们提出了一个模型，从经典激活的 M1 巨噬细胞开始，在 Th1 和促炎细胞因子的背景下加速病毒库的形成。然后，IL-4/IL-13 替代激活的 M2 巨噬细胞将参与其中，从而阻止 HIV-1 储库的扩张。最后，巨噬细胞的 IL-10 失活将导致在 HIV-1 疾病的晚期观察到免疫失败。
