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RESEARCH PRODUCT
Langerin+ DCs regulate innate IL-17 production in the oral mucosa during Candida albicans-mediated infection
Nicole JollerSarah MertensPatrizia StoitznerSalomé Leibundgut-landmannBjörn E. ClausenRoxane TussiwandTamas DolowschiakFlorian SparberLaura Lauenersubject
Malemedicine.medical_treatment2405 ParasitologyPathology and Laboratory Medicine10263 Institute of Experimental ImmunologyMonocytesMice0302 clinical medicineAnimal CellsCandida albicansBiology (General)Candida albicansMononuclear Phagocyte SystemFungal PathogensInnate Immune Systemeducation.field_of_studyEukaryotaMononuclear phagocyte systemFlow CytometryCorpus albicans3. Good healthSpectrophotometryMedical MicrobiologyCytokinesCytophotometryCellular Types10244 Institute of VirologyQH301-705.5Immune CellsImmunologyMicrobiology03 medical and health sciences1311 GeneticsGenetics1312 Molecular BiologyeducationMicrobial PathogensMolecular BiologyMouth2403 ImmunologyBlood CellsOrganismsBiology and Life SciencesDendritic CellsMolecular DevelopmentYeastMice Inbred C57BLMannose-Binding Lectins030104 developmental biologyImmunologyThy-1 Antigens570 Life sciences; biologyParasitologyImmunologic diseases. AllergyDigestive SystemDevelopmental Biology0301 basic medicineNeutrophilsPhysiologyInterleukin-1betaYeast and Fungal ModelsInterleukin-23White Blood CellsSpectrum Analysis TechniquesCandidiasis OralImmune PhysiologyLeukocytesMedicine and Health SciencesCandidaStainingbiologyInterleukin-172404 MicrobiologyCell StainingSpecific Pathogen-Free OrganismsInfectious DiseasesCytokineExperimental Organism SystemsAntigens SurfaceFemaleAnatomyPathogensResearch ArticleLangerinPopulationMycologyOpportunistic InfectionsResearch and Analysis MethodsTongueImmunityVirologymedicineAnimalsLectins C-TypeInterleukin 6Interleukin-6Mouth MucosaFungiCell BiologyRC581-607biology.organism_classificationSpecimen Preparation and TreatmentImmune Systembiology.protein2406 VirologySpleen030215 immunologydescription
The opportunistic fungal pathogen Candida albicans frequently causes diseases such as oropharyngeal candidiasis (OPC) in immunocompromised individuals. Although it is well appreciated that the cytokine IL-17 is crucial for protective immunity against OPC, the cellular source and the regulation of this cytokine during infection are still a matter of debate. Here, we directly visualized IL-17 production in the tongue of experimentally infected mice, thereby demonstrating that this key cytokine is expressed by three complementary subsets of CD90+ leukocytes: RAG-dependent αβ and γδ T cells, as well as RAG-independent ILCs. To determine the regulation of IL-17 production at the onset of OPC, we investigated in detail the myeloid compartment of the tongue and found a heterogeneous and dynamic mononuclear phagocyte (MNP) network in the infected tongue that consists of Zbtb46-Langerin- macrophages, Zbtb46+Langerin+ dendritic cells (DCs) and Ly6C+ inflammatory monocytes. Of those, the Langerin+ DC population stands out by its unique capacity to co-produce the cytokines IL-1β, IL-6 and IL-23, all of which promote IL-17 induction in response to C. albicans in the oral mucosa. The critical role of Langerin+ DCs for the innate IL-17 response was confirmed by depletion of this cellular subset in vivo, which compromised IL-17 induction during OPC. In conclusion, our work revealed key regulatory factors and their cellular sources of innate IL-17-dependent antifungal immunity in the oral mucosa.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2018-01-01 |