Titre
The c-MET receptor tyrosine kinase contributes to neutrophil-driven pathology in cutaneous leishmaniasis.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Passelli, K.
Auteure/Auteur
Prat-Luri, B.
Auteure/Auteur
Merlot, M.
Auteure/Auteur
Goris, M.
Auteure/Auteur
Mazzone, M.
Auteure/Auteur
Tacchini-Cottier, F.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1553-7374
Statut éditorial
Publié
Date de publication
2022-01
Volume
18
Numéro
1
Première page
e1010247
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Résumé
Neutrophils are the first line of defence against invading pathogens. Although neutrophils are well-known professional killers, some pathogens including Leishmania (L.) parasites survive in neutrophils, using these cells to establish infection. Manipulation of neutrophil recruitment to the infection site is therefore of interest in this cutaneous disease. The c-MET tyrosine kinase receptor was shown to promote neutrophil migration to inflamed sites. Here, we investigated the importance of c-MET expression on neutrophils in their recruitment to the infection site and the role of c-Met expression in the pathology of leishmaniasis. Following infection with L. mexicana, mice with conditional deletion of c-MET in neutrophils controlled significantly better their lesion development and parasite burden compared to similarly infected wild type mice. Our data reveal a specific role for c-MET activation in Leishmania-induced neutrophil infiltration, a process correlating with their negative role in the pathology of the diseases. We further show that c-MET phosphorylation is observed in established cutaneous lesions. Exposure to L. mexicana upregulated c-Met expression predominantly in infected neutrophils and c-Met expression influenced ROS release by neutrophils. In addition, pharmacological inhibition of c-MET, administrated once the lesion is established, induced a significant decrease in lesion size associated with diminished infiltration of neutrophils. Both genetic ablation of c-MET in neutrophils and systemic inhibition of c-MET locally resulted in higher levels of CD4+T cells producing IFNγ, suggesting a crosstalk between neutrophils and these cells. Collectively, our data show that c-MET activation in neutrophils contributes to their recruitment following infection, and that L. mexicana induction of c-MET on neutrophils impacts the local pathology associated with this disease. Our results suggest a potential use for this inhibitor in the control of the cutaneous lesion during this parasitic infection.
PID Serval
serval:BIB_F09B4A0D524F
PMID
Open Access
Oui
Date de création
2022-01-24T18:29:27.467Z
Date de création dans IRIS
2025-05-21T06:43:37Z
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Nom
35041723_BIB_F09B4A0D524F.pdf
Version du manuscrit
published
Licence
https://creativecommons.org/licenses/by/4.0
Taille
3.97 MB
Format
Adobe PDF
PID Serval
serval:BIB_F09B4A0D524F.P001
URN
urn:nbn:ch:serval-BIB_F09B4A0D524F4
Somme de contrôle
(MD5):6d55bb27dd40f06411fccd1cf248616b