Ronet, Catherine, Passelli, Katiuska, Charmoy, Melanie et al. (10 more authors) (2018) TLR2 signaling in skin non-hematopoietic cells induces early neutrophil recruitment in response to Leishmania major infection. Journal of investigative dermatology. ISSN 1523-1747
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 non-hematopoietic origin. Keratinocytes are damaged and briefly in contact with the parasites during infection. We show that TLR2 triggering by L. major is required for their secretion of neutrophil-attracting chemokines. Furthermore, TLR2 triggering by L. major phosphoglycans is critical for neutrophil recruitment impacting negatively on disease development, as shown by better control of lesion size and parasite load in Tlr2-/- compared to wild type infected mice. Conversely, restoring early neutrophil presence in Tlr2-/- 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 demonstrate a new role for TLR2-expressing non-hematopoietic skin cells in the recruitment of the first wave of neutrophils following L. major infection, a process delaying disease control.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © Elsevier, 2108. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Hull York Medical School (York) The University of York > Faculty of Sciences (York) > Biology (York) |
Depositing User: | Pure (York) |
Date Deposited: | 02 Jan 2019 11:00 |
Last Modified: | 22 Nov 2024 00:35 |
Published Version: | https://doi.org/10.1016/j.jid.2018.12.012 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1016/j.jid.2018.12.012 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:140405 |