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

• 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-4/1L-13 signaling via the common IL-4 receptor alpha chain (IL-4R alpha) on keratinocytes contributes to susceptibility during experimental CL. To address this, keratinocyte-specific IL-41R alpha-deficient (KRT14(cre) IL-4R alpha(-/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-gamma/IL-4/IL-13 cytokine production, and type 1 and type 2 antibody responses were similar between KRT14(cre) IL-4R alpha(-)(lox) and littermate control IL-4R alpha(-) (lox) BALB/c mice. An intradermal infection with low-dose L. major IL-81 and LV39 promastigotes in the ear showed results in infected KRT14(cre) IL-4R alpha(-)(/)(lox) BALB/c mice similar to those of littermate control IL-4R alpha(-)(/)(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-4/1L-13 through the IL-4R alpha chain on keratinocytes does not influence the establishment of a nonhealing Th2 immune response in BALB/c mice during L. major infection.

Ämnesord

NATURVETENSKAP  -- Biologi -- Immunologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Immunology (hsv//eng)

Nyckelord

IL-4 receptor alpha signaling; keratinocytes; Leishmania major; skin

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