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Innate immune recognition of Debaryomyces hansenii requires Dectin-1-Card9 signaling.

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Title: Innate immune recognition of Debaryomyces hansenii requires Dectin-1-Card9 signaling.
Authors: 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.
Source: Infection and immunity [Infect Immun] 2026 Sep 08; Vol. 94 (9), pp. e0015726. Date of Electronic Publication: 2026 Aug 04.
Publication Type: Journal Article
Language: English
Journal Info: 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.
MeSH Terms: 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
Abstract: 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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Nature. 2016 Dec 1;540(7631):144-149. (PMID: 27851729)
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Front Immunol. 2019 Mar 11;10:419. (PMID: 30906296)
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J Immunol. 1998 Dec 1;161(11):6198-205. (PMID: 9834106)
J Biol Chem. 2006 Dec 15;281(50):38854-66. (PMID: 17050534)
PLoS Pathog. 2005 Nov;1(3):e30. (PMID: 16304610)
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Nat Med. 2016 Jun;22(6):598-605. (PMID: 27158904)
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Cell. 2021 Feb 18;184(4):1017-1031.e14. (PMID: 33548172)
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J Microbiol Methods. 2018 Jan;144:152-156. (PMID: 29155237)
Nat Immunol. 2007 Jan;8(1):31-8. (PMID: 17159984)
Cell Rep. 2024 Mar 26;43(3):113944. (PMID: 38489265)
Nucleic Acids Res. 2019 Jul 02;47(W1):W171-W174. (PMID: 31106371)
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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
Database: MEDLINE
FullText Text:
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DbLabel: MEDLINE
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PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
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  Data: Innate immune recognition of Debaryomyces hansenii requires Dectin-1-Card9 signaling.
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  Data: <searchLink fieldCode="AU" term="%22Newhall+KP%22">Newhall KP</searchLink>; Department of Inflammation and Immunity, Cleveland Clinic Research, Cleveland, Ohio, USA.; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.<br /><searchLink fieldCode="AU" term="%22McNeer+SK%22">McNeer SK</searchLink>; Department of Inflammation and Immunity, Cleveland Clinic Research, Cleveland, Ohio, USA.; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.<br /><searchLink fieldCode="AU" term="%22Espenschied+ST%22">Espenschied ST</searchLink>; Department of Inflammation and Immunity, Cleveland Clinic Research, Cleveland, Ohio, USA.<br /><searchLink fieldCode="AU" term="%22Dolan+EG%22">Dolan EG</searchLink>; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA.<br /><searchLink fieldCode="AU" term="%22Zhou+JY%22">Zhou JY</searchLink>; Department of Inflammation and Immunity, Cleveland Clinic Research, Cleveland, Ohio, USA.<br /><searchLink fieldCode="AU" term="%22Hogan+DA%22">Hogan DA</searchLink>; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA.<br /><searchLink fieldCode="AU" term="%22Stappenbeck+TS%22">Stappenbeck TS</searchLink>; Department of Inflammation and Immunity, Cleveland Clinic Research, Cleveland, Ohio, USA.; Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
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  Data: <searchLink fieldCode="JN" term="%220246127%22">Infection and immunity</searchLink> [Infect Immun] 2026 Sep 08; Vol. 94 (9), pp. e0015726. <i>Date of Electronic Publication: </i>2026 Aug 04.
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  Data: <i>Publisher: </i><searchLink fieldCode="PB" term="%22American+Society+For+Microbiology%22">American Society For Microbiology </searchLink><i>Country of Publication: </i>United States <i>NLM ID: </i>0246127 <i>Publication Model: </i>Print-Electronic <i>Cited Medium: </i>Internet <i>ISSN: </i>1098-5522 (Electronic) <i>Linking ISSN: </i><searchLink fieldCode="IS" term="%2200199567%22">00199567 </searchLink><i>NLM ISO Abbreviation: </i>Infect Immun <i>Subsets: </i>MEDLINE
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  Data: <i>Publication</i>: Washington, DC : American Society For Microbiology<br /><i>Original Publication</i>: [Bethesda, Md.] American Society for Microbiology.
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  Data: <searchLink fieldCode="MM" term="%22Lectins%2C+C-Type%22">Lectins, C-Type*</searchLink>/<searchLink fieldCode="MM" term="%22Lectins%2C+C-Type+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Lectins%2C+C-Type%22">Lectins, C-Type*</searchLink>/<searchLink fieldCode="MM" term="%22Lectins%2C+C-Type+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Lectins%2C+C-Type%22">Lectins, C-Type*</searchLink>/<searchLink fieldCode="MM" term="%22Lectins%2C+C-Type+immunology%22">immunology</searchLink> <br /><searchLink fieldCode="MM" term="%22CARD+Signaling+Adaptor+Proteins%22">CARD Signaling Adaptor Proteins*</searchLink>/<searchLink fieldCode="MM" term="%22CARD+Signaling+Adaptor+Proteins+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22CARD+Signaling+Adaptor+Proteins%22">CARD Signaling Adaptor Proteins*</searchLink>/<searchLink fieldCode="MM" term="%22CARD+Signaling+Adaptor+Proteins+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22CARD+Signaling+Adaptor+Proteins%22">CARD Signaling Adaptor Proteins*</searchLink>/<searchLink fieldCode="MM" term="%22CARD+Signaling+Adaptor+Proteins+immunology%22">immunology</searchLink> <br /><searchLink fieldCode="MM" term="%22Debaryomyces%22">Debaryomyces*</searchLink>/<searchLink fieldCode="MM" term="%22Debaryomyces+immunology%22">immunology</searchLink> <br /><searchLink fieldCode="MM" term="%22Signal+Transduction%22">Signal Transduction*</searchLink> <br /><searchLink fieldCode="MM" term="%22Immunity%2C+Innate%22">Immunity, Innate*</searchLink><br /><searchLink fieldCode="MH" term="%22Macrophages%22">Macrophages</searchLink>/<searchLink fieldCode="MH" term="%22Macrophages+immunology%22">immunology</searchLink> ; <searchLink fieldCode="MH" term="%22Macrophages%22">Macrophages</searchLink>/<searchLink fieldCode="MH" term="%22Macrophages+microbiology%22">microbiology</searchLink> ; <searchLink fieldCode="MH" term="%22Macrophages%22">Macrophages</searchLink>/<searchLink fieldCode="MH" term="%22Macrophages+metabolism%22">metabolism</searchLink> ; <searchLink fieldCode="MH" term="%22Dectin-1%22">Dectin-1</searchLink> ; <searchLink fieldCode="MH" term="%22Innate+Immunity+Recognition%22">Innate Immunity Recognition</searchLink> ; <searchLink fieldCode="MH" term="%22Humans%22">Humans</searchLink> ; <searchLink fieldCode="MH" term="%22Animals%22">Animals</searchLink> ; <searchLink fieldCode="MH" term="%22Phagocytosis%22">Phagocytosis</searchLink> ; <searchLink fieldCode="MH" term="%22Mice%22">Mice</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: 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.
– Name: Abstract
  Label: Competing Interests
  Group: Ab
  Data: The authors declare no conflict of interest.
– Name: Ref
  Label: References
  Group: RefInfo
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(PMID: <searchLink fieldCode="PM" term="%2232234475%22">32234475)</searchLink><br />Nature. 2016 Dec 1;540(7631):144-149. (PMID: <searchLink fieldCode="PM" term="%2227851729%22">27851729)</searchLink><br />mSphere. 2017 Jun 21;2(3):. (PMID: <searchLink fieldCode="PM" term="%2228657070%22">28657070)</searchLink><br />Gut. 2017 Jun;66(6):1039-1048. (PMID: <searchLink fieldCode="PM" term="%2226843508%22">26843508)</searchLink><br />Front Immunol. 2019 Mar 11;10:419. (PMID: <searchLink fieldCode="PM" term="%2230906296%22">30906296)</searchLink><br />Cell Rep. 2012 Dec 27;2(6):1762-73. (PMID: <searchLink fieldCode="PM" term="%2223200858%22">23200858)</searchLink><br />J Immunol. 1998 Dec 1;161(11):6198-205. (PMID: <searchLink fieldCode="PM" term="%229834106%22">9834106)</searchLink><br />J Biol Chem. 2006 Dec 15;281(50):38854-66. (PMID: <searchLink fieldCode="PM" term="%2217050534%22">17050534)</searchLink><br />PLoS Pathog. 2005 Nov;1(3):e30. (PMID: <searchLink fieldCode="PM" term="%2216304610%22">16304610)</searchLink><br />Immunity. 1995 Jun;2(6):561-72. (PMID: <searchLink fieldCode="PM" term="%227540941%22">7540941)</searchLink><br />PLoS Pathog. 2015 Jul 01;11(7):e1004985. (PMID: <searchLink fieldCode="PM" term="%2226132276%22">26132276)</searchLink><br />Nature. 2024 Jun;630(8017):736-743. (PMID: <searchLink fieldCode="PM" term="%2238839956%22">38839956)</searchLink><br />Cell Host Microbe. 2015 Aug 12;18(2):183-97. (PMID: <searchLink fieldCode="PM" term="%2226269954%22">26269954)</searchLink><br />Front Microbiol. 2020 Jul 15;11:1643. (PMID: <searchLink fieldCode="PM" term="%2232760383%22">32760383)</searchLink><br />Nat Genet. 2011 Oct 09;43(11):1066-73. (PMID: <searchLink fieldCode="PM" term="%2221983784%22">21983784)</searchLink><br />Nature. 2022 Mar;603(7902):672-678. (PMID: <searchLink fieldCode="PM" term="%2235296857%22">35296857)</searchLink><br />J Exp Med. 2003 May 5;197(9):1119-24. (PMID: <searchLink fieldCode="PM" term="%2212719478%22">12719478)</searchLink><br />EMBO J. 2005 Mar 23;24(6):1277-86. (PMID: <searchLink fieldCode="PM" term="%2215729357%22">15729357)</searchLink><br />Science. 2021 Mar 12;371(6534):1154-1159. (PMID: <searchLink fieldCode="PM" term="%2233707263%22">33707263)</searchLink><br />Science. 2012 Jun 8;336(6086):1314-7. (PMID: <searchLink fieldCode="PM" term="%2222674328%22">22674328)</searchLink><br />Sci Transl Med. 2017 Mar 8;9(380):. (PMID: <searchLink fieldCode="PM" term="%2228275154%22">28275154)</searchLink><br />Nat Med. 2016 Jun;22(6):598-605. (PMID: <searchLink fieldCode="PM" term="%2227158904%22">27158904)</searchLink><br />J Biol Chem. 2004 Nov 5;279(45):46614-20. (PMID: <searchLink fieldCode="PM" term="%2215337770%22">15337770)</searchLink><br />Cell. 2021 Feb 18;184(4):1017-1031.e14. (PMID: <searchLink fieldCode="PM" term="%2233548172%22">33548172)</searchLink><br />Nature. 2014 Jan 23;505(7484):559-63. (PMID: <searchLink fieldCode="PM" term="%2224336217%22">24336217)</searchLink><br />J Microbiol Methods. 2018 Jan;144:152-156. (PMID: <searchLink fieldCode="PM" term="%2229155237%22">29155237)</searchLink><br />Nat Immunol. 2007 Jan;8(1):31-8. (PMID: <searchLink fieldCode="PM" term="%2217159984%22">17159984)</searchLink><br />Cell Rep. 2024 Mar 26;43(3):113944. (PMID: <searchLink fieldCode="PM" term="%2238489265%22">38489265)</searchLink><br />Nucleic Acids Res. 2019 Jul 02;47(W1):W171-W174. (PMID: <searchLink fieldCode="PM" term="%2231106371%22">31106371)</searchLink><br />Nat Microbiol. 2021 Dec;6(12):1493-1504. (PMID: <searchLink fieldCode="PM" term="%2234811531%22">34811531)</searchLink><br />J Immunol. 2009 Jan 15;182(2):1146-54. (PMID: <searchLink fieldCode="PM" term="%2219124758%22">19124758)</searchLink><br />Infect Immun. 2026 Sep 8;94(9):e0015726. (PMID: <searchLink fieldCode="PM" term="%2242550039%22">42550039)</searchLink><br />J Clin Invest. 2024 May 02;134(12):. (PMID: <searchLink fieldCode="PM" term="%2238696257%22">38696257)</searchLink><br />J Vis Exp. 2013 Jun 23;(76):. (PMID: <searchLink fieldCode="PM" term="%2223851980%22">23851980)</searchLink><br />Nat Med. 2023 Oct;29(10):2602-2614. (PMID: <searchLink fieldCode="PM" term="%2237749331%22">37749331)</searchLink><br />Science. 2014 Jan 3;343(6166):80-4. (PMID: <searchLink fieldCode="PM" term="%2224336569%22">24336569)</searchLink><br />Cell Host Microbe. 2019 Mar 13;25(3):377-388.e6. (PMID: <searchLink fieldCode="PM" term="%2230850233%22">30850233)</searchLink><br />Methods Mol Biol. 2016;1358:43-57. (PMID: <searchLink fieldCode="PM" term="%2226463376%22">26463376)</searchLink><br />J Leukoc Biol. 2021 Jan;109(1):161-172. (PMID: <searchLink fieldCode="PM" term="%2232941658%22">32941658)</searchLink><br />J Exp Med. 2003 May 5;197(9):1107-17. (PMID: <searchLink fieldCode="PM" term="%2212719479%22">12719479)</searchLink><br />Nature. 2021 Aug;596(7870):114-118. (PMID: <searchLink fieldCode="PM" term="%2234262174%22">34262174)</searchLink><br />Front Immunol. 2018 Aug 06;9:1836. (PMID: <searchLink fieldCode="PM" term="%2230127791%22">30127791)</searchLink><br />Annu Rev Pathol. 2016 May 23;11:127-48. (PMID: <searchLink fieldCode="PM" term="%2226907531%22">26907531)</searchLink><br />N Engl J Med. 2009 Oct 29;361(18):1760-7. (PMID: <searchLink fieldCode="PM" term="%2219864674%22">19864674)</searchLink><br />Cell Host Microbe. 2011 Dec 15;10(6):603-15. (PMID: <searchLink fieldCode="PM" term="%2222177564%22">22177564)</searchLink><br />PLoS One. 2007 Sep 19;2(9):e898. (PMID: <searchLink fieldCode="PM" term="%2217878933%22">17878933)</searchLink>
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  Data: 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
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  Data: <i>Keywords: </i>D. hansenii; Dectin-1; fungi; myeloid cells; phagocytosis
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    PhysicalDescription:
      Pagination:
        StartPage: e0015726
    Subjects:
      – SubjectFull: Macrophages immunology
        Type: general
      – SubjectFull: Macrophages microbiology
        Type: general
      – SubjectFull: Macrophages metabolism
        Type: general
      – SubjectFull: Dectin-1
        Type: general
      – SubjectFull: Innate Immunity Recognition
        Type: general
      – SubjectFull: Humans
        Type: general
      – SubjectFull: Animals
        Type: general
      – SubjectFull: Phagocytosis
        Type: general
      – SubjectFull: Mice
        Type: general
      – SubjectFull: Lectins, C-Type metabolism
        Type: general
      – SubjectFull: Lectins, C-Type genetics
        Type: general
      – SubjectFull: Lectins, C-Type immunology
        Type: general
      – SubjectFull: CARD Signaling Adaptor Proteins metabolism
        Type: general
      – SubjectFull: CARD Signaling Adaptor Proteins genetics
        Type: general
      – SubjectFull: CARD Signaling Adaptor Proteins immunology
        Type: general
      – SubjectFull: Debaryomyces immunology
        Type: general
      – SubjectFull: Signal Transduction
        Type: general
      – SubjectFull: Immunity, Innate
        Type: general
    Titles:
      – TitleFull: Innate immune recognition of Debaryomyces hansenii requires Dectin-1-Card9 signaling.
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Newhall KP
      – PersonEntity:
          Name:
            NameFull: McNeer SK
      – PersonEntity:
          Name:
            NameFull: Espenschied ST
      – PersonEntity:
          Name:
            NameFull: Dolan EG
      – PersonEntity:
          Name:
            NameFull: Zhou JY
      – PersonEntity:
          Name:
            NameFull: Hogan DA
      – PersonEntity:
          Name:
            NameFull: Stappenbeck TS
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 08
              M: 09
              Text: 2026 Sep 08
              Type: published
              Y: 2026
          Identifiers:
            – Type: issn-electronic
              Value: 1098-5522
          Numbering:
            – Type: volume
              Value: 94
            – Type: issue
              Value: 9
          Titles:
            – TitleFull: Infection and immunity
              Type: main
ResultId 1