Academic Journal
Innate immune recognition of Debaryomyces hansenii requires Dectin-1-Card9 signaling.
| Τίτλος: | Innate immune recognition of Debaryomyces hansenii requires Dectin-1-Card9 signaling. |
|---|---|
| Συγγραφείς: | Newhall KP; Department of Inflammation and Immunity, Cleveland Clinic Research, Cleveland, Ohio, USA.; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA., McNeer SK; Department of Inflammation and Immunity, Cleveland Clinic Research, Cleveland, Ohio, USA.; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA., Espenschied ST; Department of Inflammation and Immunity, Cleveland Clinic Research, Cleveland, Ohio, USA., Dolan EG; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA., Zhou JY; Department of Inflammation and Immunity, Cleveland Clinic Research, Cleveland, Ohio, USA., Hogan DA; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA., Stappenbeck TS; Department of Inflammation and Immunity, Cleveland Clinic Research, Cleveland, Ohio, USA.; Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio, USA. |
| Πηγή: | Infection and immunity [Infect Immun] 2026 Sep 08; Vol. 94 (9), pp. e0015726. Date of Electronic Publication: 2026 Aug 04. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: American Society For Microbiology Country of Publication: United States NLM ID: 0246127 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-5522 (Electronic) Linking ISSN: 00199567 NLM ISO Abbreviation: Infect Immun Subsets: MEDLINE |
| Imprint Name(s): | Publication: Washington, DC : American Society For Microbiology Original Publication: [Bethesda, Md.] American Society for Microbiology. |
| Ιατρικοί όροι (MeSH): | Lectins, C-Type*/metabolism , Lectins, C-Type*/genetics , Lectins, C-Type*/immunology , CARD Signaling Adaptor Proteins*/metabolism , CARD Signaling Adaptor Proteins*/genetics , CARD Signaling Adaptor Proteins*/immunology , Debaryomyces*/immunology , Signal Transduction* , Immunity, Innate*, Macrophages/immunology ; Macrophages/microbiology ; Macrophages/metabolism ; Dectin-1 ; Innate Immunity Recognition ; Humans ; Animals ; Phagocytosis ; Mice |
| Περίληψη: | Innate immune signaling plays a key role in host response to infection, yet the pattern recognition receptors that detect non-model gut-associated yeasts remain poorly defined. Here, we investigated macrophage sensing of Debaryomyces hansenii, a food-derived yeast that we found to be enriched within intestinal ulcers of Crohn disease (CD) patients. Using a cell surface receptor antibody screen of bone marrow-derived macrophages infected with a CD patient isolate of D. hansenii, we showed that D. hansenii-induced macrophage activation characterized by increased expression of co-stimulatory molecules, MHC-II, and pattern recognition receptors, including the C-type lectin receptor Dectin-1. Antibody blockade experiments showed both Dectin-1 and complement receptor 3 subunit CD11b were required for phagocytosis of D. hansenii, while Dectin-1 was uniquely required for production of the pro-inflammatory cytokine tumor necrosis factor (Tnf). CRISPR-Cas9-mediated deletion of Dectin-1 phenocopied antibody neutralization effects on phagocytosis. Furthermore, deletion of Dectin-1 or its downstream signaling adaptor molecule Card9 resulted in reduced Tnf secretion in response to D. hansenii. Dectin-1-mediated uptake of D. hansenii was observed in primary bone marrow-derived macrophage and dendritic cells, as well as across the spectrum of macrophage polarization states. Together, these findings define the role of Dectin-1-Card9 signaling axis in innate immune cell sensing of D. hansenii. These findings support the emerging relevance of innate immune recognition of a yeast in Crohn disease pathogenesis. |
| Competing Interests: | The authors declare no conflict of interest. |
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| Grant Information: | T32 GM152319 United States GM NIGMS NIH HHS; P20 GM113132 United States GM NIGMS NIH HHS; R01 AI168411 United States AI NIAID NIH HHS; P20-GM113132 National Institute of General Medical Sciences of the National Institutes of Health; P30 DK117469 United States DK NIDDK NIH HHS; F30 DK138707 United States DK NIDDK NIH HHS; R01 AI168411 National Institute of Allergy and Infectious Diseases of the National Institutes of Health; T32 GM152319 National Institute of General Medical Sciences of the National Institutes of Health; P30-DK117469 United States DK NIDDK NIH HHS |
| Contributed Indexing: | Keywords: D. hansenii; Dectin-1; fungi; myeloid cells; phagocytosis |
| Substance Nomenclature: | 0 (Dectin-1) 0 (Lectins, C-Type) 0 (CARD Signaling Adaptor Proteins) 0 (CARD9 protein, human) |
| Entry Date(s): | Date Created: 20260804 Date Completed: 20260908 Latest Revision: 20260912 |
| Update Code: | 20260912 |
| PubMed Central ID: | PMC13552104 |
| DOI: | 10.1128/iai.00157-26 |
| PMID: | 42550039 |
| Βάση Δεδομένων: | MEDLINE |
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