Manipulating immunity against Aspergillus fumigatus

Abstract

Efficient response to Aspergillus fumigatus requires different mechanisms. Polymorphonuclear neutrophils (PMNs) are the predominant immune cells in the acute stage of most fungal infections and play a crucial role in determining the type of pathology associated with fungal infections in different clinical settings. Dendritic cells (DC) are able to decode the fungus-associated information and translate it into different T helper (Th) and regulatory (Treg) cell responses. Functionally distinct Treg cells are activated after exposure to Aspergillus conidia. Early in infection, inflammation/Th1 reactivity is controlled by Treg cells suppressing PMNs and the immunogenic program of DC. The levels of IFN-β produced in this phase set the subsequent adaptive stage by conditioning the indoleamine 2, 3-dioxygenase (IDO)-dependent tolerogenic program of DC and the subsequent activation of tolerogenic Treg cells, which inhibit Th2 cells and prevent allergy to the fungus. Knowledge of the immunopathogenesis of Aspergillus infections may pave the way to promising strategies for immunotherapy.