Deletion of Interleukin-4 Receptor Alpha-Responsive Keratinocytes in BALB/c Mice Does Not Alter Susceptibility to Cutaneous Leishmaniasis.

Détails

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Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_29584F525AB8
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Deletion of Interleukin-4 Receptor Alpha-Responsive Keratinocytes in BALB/c Mice Does Not Alter Susceptibility to Cutaneous Leishmaniasis.
Périodique
Infection and immunity
Auteur(s)
Govender M., Hurdayal R., Martinez-Salazar B., Gqada K., Pillay S., Gcanga L., Passelli K., Nieuwenhuizen N.E., Tacchini-Cottier F., Guler R., Brombacher F.
ISSN
1098-5522 (Electronic)
ISSN-L
0019-9567
Statut éditorial
Publié
Date de publication
12/2018
Peer-reviewed
Oui
Volume
86
Numéro
12
Pages
e00710-18
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Résumé
The skin microenvironment at the site of infection plays a role in the early events that determine protective T helper 1/type 1 immune responses during cutaneous leishmaniasis (CL) infection. During CL in nonhealing BALB/c mice, early interleukin-4 (IL-4) can instruct dendritic cells for protective Th1 immunity. Additionally, keratinocytes, which are the principal cell type in the skin epidermis, have been shown to secrete IL-4 early after Leishmania major infection. Here, we investigated whether IL-4/IL-13 signaling via the common IL-4 receptor alpha chain (IL-4Rα) on keratinocytes contributes to susceptibility during experimental CL. To address this, keratinocyte-specific IL-4Rα-deficient (KRT14 <sup>cre</sup> IL-4Rα <sup>-/lox</sup> ) mice on a BALB/c genetic background were generated by gene targeting and site-specific recombination (Cre/loxP) under the control of the keratinocyte-specific krt14 locus. Following high-dose infection with L. major IL-81 and LV39 promastigotes subcutaneously in the footpad, footpad swelling, parasite burden, IFN-γ/IL-4/IL-13 cytokine production, and type 1 and type 2 antibody responses were similar between KRT14 <sup>cre</sup> IL-4Rα <sup>-/lox</sup> and littermate control IL-4Rα <sup>-/lox</sup> BALB/c mice. An intradermal infection with low-dose L. major IL-81 and LV39 promastigotes in the ear showed results in infected KRT14 <sup>cre</sup> IL-4Rα <sup>-/lox</sup> BALB/c mice similar to those of littermate control IL-4Rα <sup>-/lox</sup> BALB/c mice, with the exception of a significant decrease observed in parasite burden only at the site of LV39 infection in the ear. Collectively, our results show that autocrine and paracrine signaling of IL-4/IL-13 through the IL-4Rα chain on keratinocytes does not influence the establishment of a nonhealing Th2 immune response in BALB/c mice during L. major infection.
Mots-clé
Animals, Autocrine Communication/immunology, CD4-Positive T-Lymphocytes, Disease Susceptibility/immunology, Disease Susceptibility/parasitology, Female, Gene Deletion, Interleukin-13/immunology, Interleukin-4 Receptor alpha Subunit/genetics, Keratinocytes/immunology, Keratinocytes/parasitology, Leishmania major/immunology, Leishmaniasis, Cutaneous/immunology, Male, Mice, Mice, Inbred BALB C, Mice, Knockout, Paracrine Communication/immunology, Signal Transduction/immunology, Th2 Cells/immunology, IL-4 receptor alpha signaling, Leishmania major, keratinocytes, skin
Pubmed
Web of science
Open Access
Oui
Création de la notice
04/11/2018 15:37
Dernière modification de la notice
20/08/2019 13:09
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