| First Author | Govender M | Year | 2018 |
| Journal | Infect Immun | Volume | 86 |
| Issue | 12 | PubMed ID | 30275010 |
| Mgi Jnum | J:295304 | Mgi Id | MGI:6454243 |
| Doi | 10.1128/IAI.00710-18 | Citation | Govender M, et al. (2018) Deletion of Interleukin-4 Receptor Alpha-Responsive Keratinocytes in BALB/c Mice Does Not Alter Susceptibility to Cutaneous Leishmaniasis. Infect Immun 86(12) |
| abstractText | 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-4Ralpha) on keratinocytes contributes to susceptibility during experimental CL. To address this, keratinocyte-specific IL-4Ralpha-deficient (KRT14(cre) IL-4Ralpha(-/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-4Ralpha(-/lox) and littermate control IL-4Ralpha(-/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-4Ralpha(-/lox) BALB/c mice similar to those of littermate control IL-4Ralpha(-/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-4Ralpha chain on keratinocytes does not influence the establishment of a nonhealing Th2 immune response in BALB/c mice during L. major infection. |
