TLR7 Sensing by Neutrophils Is Critical for the Control of Cutaneous Leishmaniasis.

Autor:	Regli IB; Department of Biochemistry, WHO-Immunology Research and Training Collaborative Centre, University of Lausanne, Epalinges, Vaud, Switzerland., Passelli K; Department of Biochemistry, WHO-Immunology Research and Training Collaborative Centre, University of Lausanne, Epalinges, Vaud, Switzerland., Martínez-Salazar B; Department of Biochemistry, WHO-Immunology Research and Training Collaborative Centre, University of Lausanne, Epalinges, Vaud, Switzerland., Amore J; Otto-von-Guericke-University Magdeburg, Magdeburg and Helmholtz Centre for Infection Research, Braunschweig, Germany., Hurrell BP; Department of Biochemistry, WHO-Immunology Research and Training Collaborative Centre, University of Lausanne, Epalinges, Vaud, Switzerland., Müller AJ; Otto-von-Guericke-University Magdeburg, Magdeburg and Helmholtz Centre for Infection Research, Braunschweig, Germany., Tacchini-Cottier F; Department of Biochemistry, WHO-Immunology Research and Training Collaborative Centre, University of Lausanne, Epalinges, Vaud, Switzerland. Electronic address: fabienne.tacchini-cottier@unil.ch.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2020 Jun 09; Vol. 31 (10), pp. 107746.
DOI:	10.1016/j.celrep.2020.107746
Abstrakt:	Neutrophils are rapidly recruited to sites of infection, where they kill invading pathogens. However, they may also act as early temporary shelters, favoring subsequent pathogen dissemination in the host. We find that TLR7 sensing of the protozoan Leishmania parasite in neutrophils is essential for early parasite load regulation. Neutrophil effector functions, including reactive oxygen species (ROS) and neutrophil extracellular trap formation, are decreased in the absence of TLR7, resulting in higher parasite load and selective parasite replication in Tlr7 -/- neutrophils. Leishmania-infected Tlr7 -/- mice develop a chronic unhealing lesion, despite Th1 cell differentiation, and we show that Tlr7 -/- neutrophils alone mediate this effect. Conversely, topical treatment with a TLR7 agonist early in infection induces smaller lesion development than in untreated mice. Collectively, these findings highlight that parasite TLR7 triggering in neutrophils regulates early innate functions with major consequences on subsequent disease evolution, opening avenues for possible treatment strategies. Competing Interests: Declaration of Interests The authors declare no competing interests. (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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