Activation of innate immunity during systemic Candida infections

Abstract

Despite the increased knowledge on the mechanisms of Candida recognition and the networks of innate and adaptive host defense activated during infection, much remains to be learned regarding the distinctive modulatory effects of Candida spp on host immune responses. We showed that the chronic exposure of primary human immune cells to C. albicans primes them for subsequent stimulation with different microorganisms, mechanism that could explain the potential stimulatory effects of the fungus in hyperinflammatory conditions. We also showed that Dectin-2-/- mice were more susceptible to systemic candidiasis induced by C. albicans and C. glabrata, highlighting the role of Dectin-2 in Candida recognition. Trained immunity is a novel described phenomenon through which cells associated with the innate immune system exhibit memory characteristics upon a second encounter with a microorganism or with a microbial ligand. We demonstrated that a primary exposure to microbial ligands alters the functional fate of monocytes towards tolerance or training. Trained immunity and tolerance may have important effects on the host susceptibility to infections by inducing long-term changes in innate immune cells in the capacity of non-specifically responding to a secondary infection. This could be of exceptional interest in developing new therapeutic strategies against excessive autoinflammatory responses or for improving ineffective immune responses against an infection, by harnessing innate immune cells and their related receptors and signaling pathways (vaccine development).