Deletion of IL-4 receptor alpha-responsive keratinocytes in BALB/c mice does not alter susceptibility to cutaneous leishmaniasis. Govender, M., Hurdayal, R., Salazar, B. M., Gqada, K., Pillay, S., Gcanga, L., Passelli, K., Nieuwenhuizen, N. E, Tacchini-Cottier, F., Guler, R., & Brombacher, F. Infection and Immunity, 86(12):e00710–18, American Society for Microbiology Journals, oct, 2018. Paper doi abstract bibtex 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 non-healing BALB/c mice, early Interleukin (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 signalling via the common IL-4 receptor alpha chain (IL-4R$α$) on keratinocytes may contribute to susceptibility during experimental CL. To address this, keratinocyte-specific-IL-4R$α$ deficient (KRT14creIL-4R$α$-/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 IL81 and LV39 promastigotes subcutaneously in the footpad, footpad swelling, parasite burden, IFN-$γ$/IL-4/IL-13 cytokine production, as well as type 1 and type 2 antibody responses, were similar between KRT14creIL-4R$α$-/lox and littermate control IL-4R$α$-/lox BALB/c mice. An intradermal infection with low-dose L. major IL81 and LV39 promastigotes in the ear showed similar results in infected KRT14creIL-4R$α$-/lox BALB/c, with the exception of a significant decrease observed in the parasite burden, only at the site of LV39 infection in the ear, when compared to littermate control IL-4R$α$-/lox BALB/c mice. Collectively, our results show that autocrine and paracrine signalling of IL-4/IL-13 through the IL-4R$α$ chain on keratinocytes does not influence the establishment of a non-healing Th2 immune response in BALB/c mice during L. major infection.
@article{Govender2018,
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 non-healing BALB/c mice, early Interleukin (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 signalling via the common IL-4 receptor alpha chain (IL-4R$\alpha$) on keratinocytes may contribute to susceptibility during experimental CL. To address this, keratinocyte-specific-IL-4R$\alpha$ deficient (KRT14creIL-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 IL81 and LV39 promastigotes subcutaneously in the footpad, footpad swelling, parasite burden, IFN-$\gamma$/IL-4/IL-13 cytokine production, as well as type 1 and type 2 antibody responses, were similar between KRT14creIL-4R$\alpha$-/lox and littermate control IL-4R$\alpha$-/lox BALB/c mice. An intradermal infection with low-dose L. major IL81 and LV39 promastigotes in the ear showed similar results in infected KRT14creIL-4R$\alpha$-/lox BALB/c, with the exception of a significant decrease observed in the parasite burden, only at the site of LV39 infection in the ear, when compared to littermate control IL-4R$\alpha$-/lox BALB/c mice. Collectively, our results show that autocrine and paracrine signalling of IL-4/IL-13 through the IL-4R$\alpha$ chain on keratinocytes does not influence the establishment of a non-healing Th2 immune response in BALB/c mice during L. major infection.},
author = {Govender, Melissa and Hurdayal, Ramona and Salazar, Berenice Martinez and Gqada, Kaya and Pillay, Shandre and Gcanga, Lorna and Passelli, Katiuska and Nieuwenhuizen, Natalie E and Tacchini-Cottier, Fabienne and Guler, Reto and Brombacher, Frank},
doi = {10.1128/IAI.00710-18},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Govender et al. - 2018 - Deletion of IL-4 receptor alpha-responsive keratinocytes in BALBc mice does not alter susceptibility to cutaneo.pdf:pdf},
journal = {Infection and Immunity},
keywords = {OA,fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,original},
month = {oct},
number = {12},
pages = {e00710--18},
pmid = {30275010},
publisher = {American Society for Microbiology Journals},
title = {{Deletion of IL-4 receptor alpha-responsive keratinocytes in BALB/c mice does not alter susceptibility to cutaneous leishmaniasis.}},
url = {http://www.ncbi.nlm.nih.gov/pubmed/30275010},
volume = {86},
year = {2018}
}
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Here, we investigated whether IL-4/IL-13 signalling via the common IL-4 receptor alpha chain (IL-4R$α$) on keratinocytes may contribute to susceptibility during experimental CL. To address this, keratinocyte-specific-IL-4R$α$ deficient (KRT14creIL-4R$α$-/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 IL81 and LV39 promastigotes subcutaneously in the footpad, footpad swelling, parasite burden, IFN-$γ$/IL-4/IL-13 cytokine production, as well as type 1 and type 2 antibody responses, were similar between KRT14creIL-4R$α$-/lox and littermate control IL-4R$α$-/lox BALB/c mice. An intradermal infection with low-dose L. major IL81 and LV39 promastigotes in the ear showed similar results in infected KRT14creIL-4R$α$-/lox BALB/c, with the exception of a significant decrease observed in the parasite burden, only at the site of LV39 infection in the ear, when compared to littermate control IL-4R$α$-/lox BALB/c mice. 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