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Deletion of interleukin-4 receptor alpha-responsive keratinocytes in BALB/c mice does not alter susceptibility to cutaneous Leishmaniasis
Govender, M Hurdayal, R Martinez-Salazar, B Gqada, K Pillay, S Gcanga, L Passelli, K Nieuwenhuizen, N.E Tacchini-Cottier, F Guler, R
Govender, M
Hurdayal, R
Martinez-Salazar, B
Gqada, K
Pillay, S
Gcanga, L
Passelli, K
Nieuwenhuizen, N.E
Tacchini-Cottier, F
Guler, R
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Abstract
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 (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.
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Date
2018-11-20
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ASM Journals
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Keywords
IL-4 receptor alpha signaling,Leishmania major,keratinocytes,skin
Citation
Govender 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.