Govender, MHurdayal, RMartinez-Salazar, BGqada, KPillay, SGcanga, LPasselli, KNieuwenhuizen, N.ETacchini-Cottier, FGuler, RBrombacher, F2024-09-082024-09-082018-11-20Govender M, Hurdayal R, Martinez-Salazar B, Gqada K, Pillay S, Gcanga L, Passelli K, Nieuwenhuizen NE, Tacchini-Cottier F, Guler R, Brombacher F. Deletion of Interleukin-4 Receptor Alpha-Responsive Keratinocytes in BALB/c Mice Does Not Alter Susceptibility to Cutaneous Leishmaniasis. Infect Immun. 2018 Nov 20;86(12):e00710-18. doi: 10.1128/IAI.00710-18.https://pubmed.ncbi.nlm.nih.gov/30275010/https://doi.org/10.1128/iai.00710-18https://hdl.handle.net/11288/597465The 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 (KRT14cre IL-4Rα-/lox) 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 KRT14cre IL-4Rα-/lox and littermate control IL-4Rα-/lox BALB/c mice. An intradermal infection with low-dose L. major IL-81 and LV39 promastigotes in the ear showed results in infected KRT14cre IL-4Rα-/lox BALB/c mice similar to those of littermate control IL-4Rα-/lox 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.enIL-4 receptor alpha signalingLeishmania majorkeratinocytesskinArticle