Immunity and tolerance to infections in experimental hematopoietic transplantation

Resistance and tolerance are two types of host defense mechanisms that increase fitness in response to fungi. Several genetic polymorphisms in pattern recognition receptors, most remarkably Toll-like receptors (TLRs), have been described to influence resistance and tolerance to aspergillosis in distinct clinical settings. TLRs on dendritic cells pivotally contribute in determining the balance between immunopathology and protective immunity to the fungus. Epithelial cells also contribute to this balance via selected TLRs converging on indoleamine-2,3-dioxygenase (IDO). Studies in experimental hematopoietic transplantation confirmed the dichotomy of pathways leading to resistance and tolerance to the fungus providing new insights on the relative contribution of the hematopoietic/nonhematopoietic compartments.This work was supported by the Specific Targeted Research Project SYBARIS (LSHE-CT-2006), contract number 242220 (FP7), and by the Italian Project PRIN 2007KLCKP8_004. Agostinho Carvalho and Cristina Cunha were financially supported by fellowships from Fundação para a Ciência e Tecnologia, Portugal (contracts SFRH/BPD/46292/2008 and SFRH/BD/65962/2009 respectively)