Regulation of host-microbe interactions at oral mucosal barriers by type 17 immunity

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Science Immunology  03 Jan 2020:
Vol. 5, Issue 43, eaau4594
DOI: 10.1126/sciimmunol.aau4594


  • Fig. 1 Histology of the oral mucosa, a barrier for environmental stimuli and commensal microbiota.

    The oral mucosa is a frequent site of first encounter. Airborne particles (allergens), commensal microbes, and food enter the mouth before transiting to the gastrointestinal tract or airway. The oral mucosa is composed of a stratified squamous epithelium with varying characteristics at different oral anatomical locations. Lining epithelium (buccal, inner lip, and floor of mouth) is multilayered, nonkeratinized, and with rich vascularity in the submucosal areas. Immune cells are scattered within and underlying the epithelium. In the dorsum and lateral borders of the tongue, the oral mucosa becomes specialized, with discrete formations called papillae. Within the papillae are taste buds, the chemoreceptors of taste. Within the tonsils, the epithelium becomes invaginated, forming crypts. Crypt epithelium is often just a single layer with interspersed M cells, which can sample antigens and transfer them to underlying immune cells, which form germinal centers. Another area of vulnerable epithelium lies in the gingival crevice. Crevicular epithelium becomes very thin at the base of the pocket, where it connects to the tooth surface. This epithelial barrier is constantly exposed to the tooth-adherent microbial biofilm. Immune cells are abundant in this region, and neutrophils continuously transmigrate through from the tissue into the crevice.

  • Fig. 2 Oral mucosal histology.

    Oral microbiota are linked to the initiation and/or pathogenesis of systemic diseases such as colon cancer, infectious endocarditis, ventilator-associated pneumonia, and Alzheimer’s disease. Periodontitis has been associated with systemic conditions such as cardiovascular disease, diabetes, pregnancy complications, and RA.

  • Fig. 3 Regulation/function of TH17 in periodontal immunity and inflammation.

    In health, the trigger for TH17 cell accumulation in the gingiva is ongoing damage that occurs during mastication. Resulting local tissue damage triggers IL-6 production from epithelial cells, which induces TH17 cell accumulation in an antigen-dependent manner. These health-associated TH17 cells secrete IL-17 and mediate IL-17–dependent protective barrier responses, such as antimicrobial defense. In periodontitis, TH17 cells are expanded in the gingiva in response to a dysbiotic microbiome. Disease-associated microbiota trigger IL-6– and IL-23–dependent accumulation of TH17 cells. Disease-causing TH17 cells drive periodontal bone loss through excessive neutrophil recruitment and related immunopathology.

  • Fig. 4 Regulation/function of IL-17–secreting cells during candidiasis.

    C. albicans is a dimorphic commensal fungus that colonizes the human oral cavity. In health, this organism is found mainly in an avirulent yeast form and triggers little or no immune activity in the oral mucosa. Upon conversion to a hyphal state, C. albicans exposes β-glucans in the cell wall that activates the dectin-1/CARD9 pathway in antigen-presenting cells (APCs). APCs consequently secrete TH17-skewing cytokines such as IL-1, IL-6, and IL-23, driving IL-17 production from antigen-specific TH17 cells. Hyphae also secrete the peptide candidalysin, which damages oral epithelial cells and triggers secretion of DAMPs (damage-associated molecular patterns) such as IL-1 and IL-36. These signals activate innate IL-17–producing cells. IL-17 binds to its receptor on oral epithelial cells and induces antimicrobial effectors, including CXC chemokines and G-CSF that promote a neutrophil response and BDs that have direct fungicidal activity.


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