Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB T2N 4Z6, Canada; Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4Z6, Canada; Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4Z6, Canada.
Departamento de Bioquímica e Imunologia - ICB - Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270901, Brazil.
Cell Host Microbe. 2020 May 13;27(5):752-768.e7. doi: 10.1016/j.chom.2020.03.011. Epub 2020 Apr 15.
The impact of T helper (Th) 1 versus Th2 immunity on intracellular infections is attributed to classical versus alternative activation of macrophages leading to resistance or susceptibility. However, observations in multiple infectious settings demonstrate deficiencies in mediators of Th1-Th2 immunity, which have paradoxical or no impact. We report that prior to influencing activation, Th1/Th2 immunity first controls the size of the permissive host cell reservoir. During early Leishmania infection of the skin, IFN-γ- or STAT6-mediated changes in phagocyte activation were counteracted by changes in IFN-γ-mediated recruitment of permissive CCR2 monocytes. Monocytes were required for early parasite expansion and acquired an alternatively activated phenotype despite the Th1 dermal environment required for their recruitment. Surprisingly, STAT6 did not enhance intracellular parasite proliferation, but rather modulated the size and permissiveness of the monocytic host cell reservoir via regulation of IFN-γ and IL-10. These observations expand our understanding of the Th1-Th2 paradigm during infection.
辅助性 T 细胞 (Th) 1 与 Th2 免疫对细胞内感染的影响归因于经典或替代激活的巨噬细胞，导致抵抗或易感性。然而，在多种感染环境中的观察表明，Th1-Th2 免疫的介质存在缺陷，这些缺陷具有矛盾或没有影响。我们报告说，在影响激活之前，Th1/Th2 免疫首先控制允许宿主细胞库的大小。在皮肤早期感染利什曼原虫时，吞噬细胞激活的 IFN-γ 或 STAT6 介导的变化被 IFN-γ 介导的允许性 CCR2 单核细胞募集的变化所抵消。单核细胞是早期寄生虫扩张所必需的，并且尽管招募它们需要 Th1 皮肤环境，但获得了替代性激活的表型。令人惊讶的是，STAT6 并没有增强细胞内寄生虫的增殖，而是通过调节 IFN-γ 和 IL-10 来调节单核细胞宿主细胞库的大小和允许性。这些观察结果扩展了我们对感染期间 Th1-Th2 范例的理解。
