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Publication : Th1-Th2 Cross-Regulation Controls Early Leishmania Infection in the Skin by Modulating the Size of the Permissive Monocytic Host Cell Reservoir.

First Author  Carneiro MB Year  2020
Journal  Cell Host Microbe Volume  27
Issue  5 Pages  752-768.e7
PubMed ID  32298657 Mgi Jnum  J:323840
Mgi Id  MGI:6877180 Doi  10.1016/j.chom.2020.03.011
Citation  Carneiro MB, et al. (2020) Th1-Th2 Cross-Regulation Controls Early Leishmania Infection in the Skin by Modulating the Size of the Permissive Monocytic Host Cell Reservoir. Cell Host Microbe 27(5):752-768.e7
abstractText  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-gamma- or STAT6-mediated changes in phagocyte activation were counteracted by changes in IFN-gamma-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-gamma and IL-10. These observations expand our understanding of the Th1-Th2 paradigm during infection.
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