Balancing inflammation and tolerance in vivo through dendritic cells by the commensal Candida albicans

Mucosal Immunol. 2009 Jul;2(4):362-74. doi: 10.1038/mi.2009.17. Epub 2009 May 6.


We analyzed the contribution of intracellular signaling to the functional plasticity of dendritic cells (DCs) presenting Candida albicans, a human commensal associated with severe diseases. Distinct intracellular pathways were activated by recognition of different fungal morphotypes in distinct DC subsets and in Peyer's patches DCs. Inflammatory DCs initiated Th17/Th2 responses to yeasts through the adaptor myeloid differentiation factor-88 (MyD88), whereas tolerogenic DCs activate Th1/T regulatory cell (Treg) differentiation programs to hyphae involving Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF) as an intermediary of signaling. In addition, signal transducer and activator of transcription 3 (STAT3), affecting the balance between canonical and non-canonical activation of nuclear factor-kappaB (NF-kappaB) and 2,3 indoleamine dioxygenase (IDO), pivotally contributed to DC plasticity and functional specialization. As Candida-induced tolerogenic DCs ameliorated experimental colitis, our data qualify Candida as a commensal with immunoregulatory activity, resulting from the orchestrated usage of multiple, yet functionally distinct, receptor-signaling pathways in DCs. Ultimately, affecting the local Th17/Treg balance might likely be exploited by the fungus for either commensalism or pathogenicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport / immunology
  • Adaptor Proteins, Vesicular Transport / metabolism
  • Candida albicans / immunology*
  • Candidiasis / immunology*
  • Dendritic Cells / immunology*
  • Dendritic Cells / microbiology
  • Humans
  • Immune Tolerance*
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / immunology
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
  • Inflammation / immunology*
  • Inflammation / microbiology
  • Myeloid Differentiation Factor 88 / immunology
  • Myeloid Differentiation Factor 88 / metabolism
  • NF-kappa B / immunology
  • NF-kappa B / metabolism
  • Protein Kinases / immunology
  • Protein Kinases / metabolism
  • STAT3 Transcription Factor / immunology
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / immunology
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / microbiology
  • Th1 Cells / immunology
  • Th1 Cells / microbiology
  • Th2 Cells / immunology
  • Th2 Cells / microbiology


  • Adaptor Proteins, Vesicular Transport
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Myeloid Differentiation Factor 88
  • NF-kappa B
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • TICAM1 protein, human
  • Protein Kinases