title: Early activation of the interleukin-23-17 axis in a murine model of oropharyngeal candidiasis.
abstract: Candida albicans is an oral commensal yeast that causes oropharyngeal candidiasis (OPC) in immunocompromised individuals. The immunological pathways involved in OPC have been revisited after the interleukin-17 (IL-17) pathway was implicated in fungal immunity. We studied immediate (<24 h) and adaptive (3-6 day) IL-12 and IL-23-17 pathway activation in naive p40(-/-) mice, which lack IL-12 and IL-23 and develop severe, chronic OPC upon oral inoculation with C. albicans. Macrophages from p40(-/-) mice were less efficient than C57BL/6J controls at killing C. albicans in vitro but very low numbers in the oral mucosae of infected C57BL/6J mice suggest that they are not critical in vivo, at least in this strain. Migration of macrophages to regional lymph nodes of infected p40(-/-) mice was impaired; however, dendritic cell migration was not affected. Recombinant IL-12 therapy provided only temporary relief from OPC, suggesting that IL-23 is required for full protection. In C57BL/6J mice, but not p40(-/-) mice, messenger RNAs encoding IL-23p19 and IL-17 were induced in the oral mucosa within 24 h of infection (6 ± 0.6 and 12 ± 2.7-fold). By day 6 of infection in C57BL/6J mice, IL-17A messenger RNA level had increased 5.1 ± 1.8 and 83 ± 21-fold in regional lymph nodes and oral tissues respectively. Ablation of p40 was associated with delayed or abrogated induction of IL-17A pathway targets (monocyte chemoattractant protein-1, IL-6 and macrophage inflammatory protein-2), and a lack of organized recruitment of neutrophils to the infected oral mucosa. Overall our data show that the IL-23-17A axis is activated early in the oral mucosae of immunologically naive mice with OPC.
authors.affiliation: School of Dentistry, the University of Queensland, Brisbane, Australia.
authors.forename: J M
authors.initials: JM
authors.lastname: Saunus
authors.forename: S A
authors.initials: SA
authors.lastname: Wagner
authors.forename: M A
authors.initials: MA
authors.lastname: Matias
authors.forename: Y
authors.initials: Y
authors.lastname: Hu
authors.forename: Z M
authors.initials: ZM
authors.lastname: Zaini
authors.forename: C S
authors.initials: CS
authors.lastname: Farah
mesh_terms: D000818:Animals; D002180:Candidiasis, Oral / Q000235:genetics / Q000276:immunology*; D018932:Chemokine CCL2 / Q000276:immunology; D054426:Chemokine CXCL2 / Q000276:immunology; D002908:Chronic Disease; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D007113:Immunity, Innate; D018664:Interleukin-12 / Q000276:immunology*; D053762:Interleukin-12 Subunit p40 / Q000172:deficiency; D020381:Interleukin-17 / Q000276:immunology*; D053759:Interleukin-23 / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009061:Mouth Mucosa / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D010587:Phagocytosis; D011994:Recombinant Proteins; D013047:Specific Pathogen-Free Organisms; D057705:Transendothelial and Transepithelial Migration
chemical_list: D018932:Chemokine CCL2; D054426:Chemokine CXCL2; D053762:Interleukin-12 Subunit p40; D020381:Interleukin-17; D053759:Interleukin-23; D011994:Recombinant Proteins; D018664:Interleukin-12