Mucosal Immunol. 2009 May 6. [Epub ahead of print]
Balancing inflammation and tolerance in vivo through dendritic cells by the commensal Candida albicans.
Bonifazi P, Zelante T, D'Angelo C, De Luca A, Moretti S, Bozza S, Perruccio K, Iannitti RG, Giovannini G, Volpi C, Fallarino F, Puccetti P, Romani L. Department of Experimental Medicine and Biochemical Sciences, Microbiology Section, University of Perugia, Perugia, Italy.
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.Mucosal Immunology advance online publication 6 May 2009. doi:10.1038/mi.2009.17.
PMID: 19421183 [PubMed - as supplied by publisher]
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