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

Details

Serval ID
serval:BIB_2F72D18D6436
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
TLR7 Sensing by Neutrophils Is Critical for the Control of Cutaneous Leishmaniasis.
Journal
Cell reports
Author(s)
Regli I.B., Passelli K., Martínez-Salazar B., Amore J., Hurrell B.P., Müller A.J., Tacchini-Cottier F.
ISSN
2211-1247 (Electronic)
Publication state
Published
Issued date
09/06/2020
Peer-reviewed
Oui
Volume
31
Number
10
Pages
107746
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
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 <sup>-/-</sup> neutrophils. Leishmania-infected Tlr7 <sup>-/-</sup> mice develop a chronic unhealing lesion, despite Th1 cell differentiation, and we show that Tlr7 <sup>-/-</sup> 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.
Keywords
Leishmania, Leishmania major, NETs, ROS, TLR agonists, Toll-like receptor 7, Toll-like receptors, imiquimod, neutropenic mice, neutrophils
Pubmed
Web of science
Open Access
Yes
Create date
25/06/2020 16:13
Last modification date
26/01/2022 6:36
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