The cell biology of the innate immune response to Aspergillus fumigatus

The development of invasive aspergillosis is a feared complication for immunocompromised patients. Despite the use of antifungal agents with excellent bioactivity, the morbidity and mortality rates for invasive aspergillosis remain unacceptably high. Defects within the innate immune response portend the highest risk for patients, but detailed knowledge of molecular pathways in neutrophils and macrophages in response to this fungal pathogen is lacking. Phagocytosis of fungal spores is a key step that places the pathogen into a phagosome, a membrane-delimited compartment that undergoes maturation and ultimately delivers antigenic material to the class II MHC pathway. We review the role of Toll-like receptor 9 (TLR9) in phagosome maturation of Aspergillus fumigates-containing phagosomes. Advanced imaging modalities and the development of fungal-like particles are promising tools that will aid in the dissection of the molecular mechanism to fungal immunity.