Immunity and tolerance to fungi in hematopoietic transplantation: Principles and perspectives

Resistance and tolerance are two complementary host defense mechanisms that increase fitness in response to low-virulence fungi. Resistance is meant to reduce pathogen bur-den during infection through innate and adaptive immune mechanisms, whereas toler-ance mitigates the substantial cost of resistance to host fitness through a multitude of anti-inflammatory mechanisms, including immunological tolerance. In experimental fun-gal infections, both defense mechanisms are activated through the delicate equilibrium betweenTh1/Th17 cells, which provide antifungal resistance, and regulatoryT cells limiting the consequences of the ensuing inflammatory pathology. Indoleamine 2,3-dioxygenase (IDO), a rate-limiting enzyme in the tryptophan catabolism, plays a key role in induc-tion of tolerance against fungi. Both hematopoietic and non-hematopoietic compartments contribute to the resistance/tolerance balance against Aspergillus fumigatus via the involve-ment of selected innate receptors converging on IDO. Several genetic polymorphisms in pattern recognition receptors influence resistance and tolerance to fungal infections in human hematopoietic transplantation. Thus, tolerance mechanisms may be exploited for novel diagnostics and therapeutics against fungal infections and diseases. © 2012 Carvalho, Cunha, Bozza, Moretti, Massi-Benedetti, Bis-toni, Aversaand Romani.