TLR2 signaling in skin non-hematopoietic cells induces early neutrophil recruitment in response to Leishmania major infection

Catherine Ronet; Katiuska Passelli; Melanie Charmoy; Leo Scarpellino; Elmarie Myburgh; Yazmin  Hauyon La Torre; Salvatore Turco; Jeremy Charles Mottram; Nicolas Fasel; Sanjiv A. Luther; Stephen M. Beverley; Pascal Launois; Fabienne Tacchini-Cottier

doi:10.1016/j.jid.2018.12.012

TLR2 signaling in skin non-hematopoietic cells induces early neutrophil recruitment in response to Leishmania major infection

Catherine Ronet, Katiuska Passelli, Melanie Charmoy, Leo Scarpellino, Elmarie Myburgh, Yazmin Hauyon La Torre, Salvatore Turco, Jeremy Charles Mottram, Nicolas Fasel, Sanjiv A. Luther, Stephen M. Beverley, Pascal Launois, Fabienne Tacchini-Cottier

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Journal	Journal of investigative dermatology
Early online date	27 Dec 2018
DOIs	https://doi.org/10.1016/j.jid.2018.12.012
Publication status	Published - 27 Dec 2018

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10.1016/j.jid.2018.12.012

Mottram - Ronet JID 2018
© Elsevier, 2108. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy.
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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. (2018). TLR2 signaling in skin non-hematopoietic cells induces early neutrophil recruitment in response to Leishmania major infection. Journal of investigative dermatology. https://doi.org/10.1016/j.jid.2018.12.012

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title = "TLR2 signaling in skin non-hematopoietic cells induces early neutrophil recruitment in response to Leishmania major infection",

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.",

author = "Catherine Ronet and Katiuska Passelli and Melanie Charmoy and Leo Scarpellino and Elmarie Myburgh and {Hauyon La Torre}, Yazmin and Salvatore Turco and Mottram, {Jeremy Charles} and Nicolas Fasel and Luther, {Sanjiv A.} and Beverley, {Stephen M.} and Pascal Launois and Fabienne Tacchini-Cottier",

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Ronet, C, Passelli, K, Charmoy, M, Scarpellino, L, Myburgh, E, Hauyon La Torre, Y, Turco, S, Mottram, JC, Fasel, N, Luther, SA, Beverley, SM, Launois, P & Tacchini-Cottier, F 2018, 'TLR2 signaling in skin non-hematopoietic cells induces early neutrophil recruitment in response to Leishmania major infection', Journal of investigative dermatology. https://doi.org/10.1016/j.jid.2018.12.012

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T1 - TLR2 signaling in skin non-hematopoietic cells induces early neutrophil recruitment in response to Leishmania major infection

AU - Ronet, Catherine

AU - Passelli, Katiuska

AU - Charmoy, Melanie

AU - Scarpellino, Leo

AU - Myburgh, Elmarie

AU - Hauyon La Torre, Yazmin

AU - Turco, Salvatore

AU - Mottram, Jeremy Charles

AU - Fasel, Nicolas

AU - Luther, Sanjiv A.

AU - Beverley, Stephen M.

AU - Launois, Pascal

AU - Tacchini-Cottier, Fabienne

N1 - © Elsevier, 2108. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy.

PY - 2018/12/27

Y1 - 2018/12/27

N2 - 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.

AB - 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.

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DO - 10.1016/j.jid.2018.12.012

M3 - Article

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SN - 0022-202X

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