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

2009; Elsevier BV; Volume: 2; Issue: 4 Linguagem: Inglês

10.1038/mi.2009.17

1935-3456

Pierluigi Bonifazi, Teresa Zelante, C. D’Angelo, Antonella De Luca, Silvia Moretti, Silvia Bozza, Katia Perruccio, Rossana G. Iannitti, Gloria Giovannini, Claudia Volpi, Francesca Fallarino, Paolo Puccetti, Luigina Romani,

T-cell and B-cell Immunology

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.