TLR2 Signaling in Skin Nonhematopoietic Cells Induces Early Neutrophil Recruitment in Response to Leishmania major Infection.

Details

Serval ID
serval:BIB_8AC775CA2A74
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
TLR2 Signaling in Skin Nonhematopoietic Cells Induces Early Neutrophil Recruitment in Response to Leishmania major Infection.
Journal
The Journal of investigative dermatology
Author(s)
Ronet C., Passelli K., Charmoy M., Scarpellino L., Myburgh E., Hauyon La Torre Y., Turco S., Mottram J.C., Fasel N., Luther S.A., Beverley S.M., Launois P., Tacchini-Cottier F.
ISSN
1523-1747 (Electronic)
ISSN-L
0022-202X
Publication state
Published
Issued date
06/2019
Peer-reviewed
Oui
Volume
139
Number
6
Pages
1318-1328
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Neutrophils are rapidly recruited to the mammalian skin in response to infection with the cutaneous Leishmania pathogen. The parasites use neutrophils to establish the disease; however, the signals driving early neutrophil recruitment are poorly known. Here, we identified the functional importance of TLR2 signaling in this process. Using bone marrow chimeras and immunohistology, we identified the TLR2-expressing cells involved in this early neutrophil recruitment to be of nonhematopoietic origin. Keratinocytes are damaged and briefly in contact with the parasites during infection. We show that TLR2 triggering by Leishmania major is required for their secretion of neutrophil-attracting chemokines. Furthermore, TLR2 triggering by L. major phosphoglycans is critical for neutrophil recruitment to negatively affect disease development, as shown by better control of lesion size and parasite load in Tlr2 <sup>-/-</sup> compared with wild-type infected mice. Conversely, restoring early neutrophil presence in Tlr2 <sup>-/-</sup> mice through injection of wild-type neutrophils or CXCL1 at the onset of infection resulted in delayed disease resolution comparable to that observed in wild-type mice. Taken together, our data show a crucial role for TLR2-expressing nonhematopoietic skin cells in the recruitment of the first wave of neutrophils after L. major infection, a process that delays disease control.
Keywords
Animals, Bone Marrow Transplantation, Cell Communication/immunology, Chemokine CXCL1/immunology, Chemokine CXCL1/metabolism, Disease Models, Animal, Humans, Keratinocytes/immunology, Keratinocytes/metabolism, Leishmania major/immunology, Leishmania major/isolation & purification, Leishmaniasis, Cutaneous/immunology, Leishmaniasis, Cutaneous/parasitology, Leishmaniasis, Cutaneous/pathology, Mice, Mice, Knockout, Neutrophil Infiltration, Neutrophils/immunology, Parasite Load, Signal Transduction/genetics, Signal Transduction/immunology, Skin/cytology, Skin/immunology, Skin/parasitology, Skin/pathology, Toll-Like Receptor 2/genetics, Toll-Like Receptor 2/immunology, Toll-Like Receptor 2/metabolism, Transplantation Chimera
Pubmed
Web of science
Open Access
Yes
Create date
23/01/2019 12:01
Last modification date
26/06/2020 6:21
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