title: Nociceptive Sensory Fibers Drive Interleukin-23 Production from CD301b+ Dermal Dendritic Cells and Drive Protective Cutaneous Immunity.
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.
authors.affiliation: Department of Dermatology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Sakeen W
authors.initials: SW
authors.lastname: Kashem
authors.affiliation: Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Maureen S
authors.initials: MS
authors.lastname: Riedl
authors.affiliation: Department of Dermatology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Yao
authors.affiliation: Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Christopher N
authors.initials: CN
authors.lastname: Honda
authors.affiliation: Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Lucy
authors.initials: L
authors.lastname: Vulchanova
authors.affiliation: Department of Dermatology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: dankaplan@pitt.edu.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Kaplan
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000276:immunology / Q000502:physiology; D002177:Candidiasis / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D020405:Dermis / Q000166:cytology; D005434:Flow Cytometry; D054884:Host-Pathogen Interactions / Q000276:immunology; D007109:Immunity / Q000235:genetics / Q000276:immunology*; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053759:Interleukin-23 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D011984:Sensory Receptor Cells / Q000276:immunology* / Q000378:metabolism; D012867:Skin / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics / Q000276:immunology
chemical_list: D020381:Interleukin-17; D053759:Interleukin-23; D037181:Lectins, C-Type; C464940:MGL2 protein, mouse; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018015:Receptors, Calcitonin Gene-Related Peptide