Immune regulation by fungal strain diversity in inflammatory bowel disease

Abstract

Fungal strain-level diversity defines host-mycobiota interactions and inflammation in inflammatory bowel disease.

Immunosurveillance of Candida albicans commensalism by the adaptive immune system

“…Accordingly, C. albicans -specific Th17 cells are increased in the blood of CD patients 14 , presumably as a consequence of enhanced microbial translocation in the inflamed and barrier-disrupted gut, and their frequencies correlate with the faecal abundance of C. albicans in intensive care unit patients 35 . Most recently, the pathogenicity of gut-colonizing C. albicans isolates was identified as a decisive factor for enhanced inflammation in IBD patients 103 . In light of the harmful rather than protective effects of IL-17 blockade in inflammatory bowel disease (IBD) patients 104 , the role of C albicans -specific Th17 cells in CD pathogenesis remains controversial.…”

Friendly fungi: symbiosis with commensal Candida albicans

“…Pseudomonas aeruginosa after C. albicans systemic priming [56] Staphylococcus aureus after C. albicans systemic priming S. aureus, requires tonic stimulation [55] Citrobacter rodentium [65] Protection against intestinal inflammation Mouse Fluconazole treatment (DSS) [66] Monocolonization (DSS) [17] Mucosal vs luminal (DSS) [65] Protection against airway inflammation Mouse Fluconazole treatment (HDM) [66] Fluconazole treatment, CX3CR1 cell dependent [67] Socialization behavior Mouse IL-17 dependent [65] Increased circulating granulocytes Mouse Rewilding with fungal acquisition [58] Promotes intestinal inflammation Mouse/human CX3CR1 cell defects (Crohn's disease) [75] Mouse Hyphal-locked [53] Mouse/human Candidalysin-dependent, highly cell-damaging strains (ulcerative colitis) [69] Human Increased IgA hyphal targets (Crohn's disease) [98] Human Th17 cells [54] Human Fecal transplant (ulcerative colitis) [99] Mouse/human Malassezia (Crohn's disease) [73] Promotes airway inflammation Human COPD, cystic fibrosis, ABPA [54] Mouse Requires tonic stimulation (HDM) [55] Mouse Candidalysin dependent [81] Promotes While neutrophils appear to be essential for colonization-induced protection, the necessity for adaptive immune components, including antibody-producing B cells and fungus-specific T cells, differs between studies. For example, C. albicans cells of the standard strain (SC5314) that were passaged in the gut of laboratory mice lost their ability to undergo filamentous growth, a key morphological change induced by the host environment [60,61], yet provided increased colonization-induced protection in both C57BL/6 wild-type and Rag1 −/− mice (the latter being deficient in both B and T cells) [56].…”

“…This response might be protective, as treatment with the anti-IL-17A monoclonal antibody eculizumab caused increased disease symptoms compared with placebo controls [68]. Also, recent studies have highlighted C. albicans strain-to-strain heterogeneity in driving intestinal inflammation, suggesting that additional analysis of immunogenic and toxic protein expression by C. albicans in the commensal state is warranted [69]. For instance, C. albicans strains with high macrophage-damaging capacity are more enriched among ulcerative colitis patients than in individuals without IBD, and reconstituting mice with these strains enhances their susceptibility to DSS-induced intestinal injury [69].…”

“…Also, recent studies have highlighted C. albicans strain-to-strain heterogeneity in driving intestinal inflammation, suggesting that additional analysis of immunogenic and toxic protein expression by C. albicans in the commensal state is warranted [69]. For instance, C. albicans strains with high macrophage-damaging capacity are more enriched among ulcerative colitis patients than in individuals without IBD, and reconstituting mice with these strains enhances their susceptibility to DSS-induced intestinal injury [69]. Therefore, macrophage-damaging capability may be a major determinant of strainspecific disease induction by C. albicans.…”

Bile Acid Regulates Mononuclear Phagocytes and T Helper 17 Cells to Control Candida albicans in the Intestine

“…Furthermore, TCA alters the relative abundance of certain commensal bacterial members and the expression of antifungal peptides in the colon of mice that had increased fungal colonization and dissemination [ 14 ]. Since innate (neutrophils and macrophages) and adaptive immune cells (T helper 1 and 17 cells) contribute to antifungal defense in the intestine [ 5 , 8 , 15 , 16 ], we aim to understand if TCA dysregulates mucosal immune response to promote CA colonization in the intestine. Our results suggest that TCA treatment significantly decreased the mononuclear phagocytes and T helper 17 cells that play an important role in antifungal defense against CA in the intestine.…”