Nociceptive Sensory Fibers Drive Interleukin-23 Production from CD301b+ Dermal Dendritic Cells and Drive Protective Cutaneous Immunity

Sakeen W. Kashem, Maureen S. Riedl, Chen Yao, Christopher N. Honda, Lucy Vulchanova, Daniel H. Kaplan

Research output: Contribution to journalArticlepeer-review

137 Scopus citations

Abstract

Innate resistance to Candida albicans in mucosal tissues requires the production of interleukin-17A (IL-17A) by tissue-resident cells early during infection, but the mechanism of cytokine production has not been precisely defined. In the skin, we found that dermal γδ T cells were the dominant source of IL-17A during C. albicans infection and were required for pathogen resistance. Induction of IL-17A from dermal γδ T cells and resistance to C. albicans required IL-23 production from CD301b+ dermal dendritic cells (dDCs). In addition, we found that sensory neurons were directly activated by C. albicans. Ablation of sensory neurons increased susceptibility to C. albicans infection, which could be rescued by exogenous addition of the neuropeptide CGRP. These data define a model in which nociceptive pathways in the skin drive production of IL-23 by CD301b+ dDCs resulting in IL-17A production from γδ T cells and resistance to cutaneous candidiasis.

Original languageEnglish (US)
Article number3159
Pages (from-to)515-526
Number of pages12
JournalImmunity
Volume43
Issue number3
DOIs
StatePublished - Sep 15 2015

Bibliographical note

Funding Information:
We thank the laboratories of Marc Jenkins and Daniel Mueller (University of Minnesota) for Tcra −/− mice, Nico Ghilardi (Genentech) for Il23a −/− mice, Lloyd Miller (Johns Hopkins) for Tcrd −/− mice, Akiko Iwasaki and Yosuke Kumamoto (Yale University) for Mgl2-DTR mice, and Immo Prinz (Hannover Medical School) and Bryce Binstadt (University of Minnesota) for Il17af −/− mice. B. Chicoine provided technical assistance. We also thank the University of Minnesota Research Animal Resources staff for expert animal care and P. Champoux and T. Martin of the Flow Cytometry Core Facility at the Center for Immunology for assistance flow cytometry experiments. This work was supported by grants from the NIH (AR067187 and AR060744) to D.H.K., who is also supported by the Al Zelickson Family endowed professorship. S.W.K. was supported by the University of Minnesota NIH MSTP grant T32 GM008244, Immunology Training Grant T32 AI007313, and University of Minnesota CTSI Translational Research Development Program Grant UL1TR000114.

Publisher Copyright:
© 2015 Elsevier Inc.

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