ABSTRACT
Aspergillus fumigatus, an important pulmonary fungal pathogen causing several diseases collectively called aspergillosis, relies on asexual spores (conidia) for initiating host infection. Here, we used a phylogenomic approach to compare proteins in the conidial surface of A. fumigatus, two closely related non-pathogenic species, Aspergillus fischeri and Aspergillus oerlinghausenensis, and the cryptic pathogen Aspergillus lentulus. After identifying 62 proteins uniquely expressed on the A. fumigatus conidial surface, we assessed null mutants for 42 genes encoding conidial proteins. Deletion of 33 of these genes altered susceptibility to macrophage killing, penetration and damage to epithelial cells, and cytokine production. Notably, a gene that encodes glycosylasparaginase, which modulates levels of the host pro-inflammatory cytokine IL-1ß, is important for infection in an immunocompetent murine model of fungal disease. These results suggest that A. fumigatus conidial surface proteins and effectors are important for evasion and modulation of the immune response at the onset of fungal infection.
ABSTRACT
Aspergillus fumigatus , an important pulmonary fungal pathogen causing several diseases collectively called aspergillosis, relies on asexual spores or conidia for initiating host infection. Here, we used a phylogenomic approach to compare proteins in the conidial surface of A. fumigatus , two closely related non-pathogenic species, Aspergillus fischeri and Aspergillus oerlinghausenensis , and the cryptic pathogen Aspergillus lentulus . After identifying 62 proteins uniquely expressed on the A. fumigatus conidial surface, we deleted 42 genes encoding conidial proteins. We found deletion of 33 of these genes altered susceptibility to macrophage killing, penetration and damage to epithelial cells, and cytokine production. Notably, a gene that encodes glycosylasparaginase, which modulates levels of the host pro-inflammatory cytokine IL-1ß, is important for infection in an immunocompetent murine model of fungal disease. These results suggest that A. fumigatus conidial surface proteins and effectors are important for evasion and modulation of the immune response at the onset of fungal infection.
ABSTRACT
Pulmonary infections caused by the mould pathogen Aspergillus fumigatus are a major cause of morbidity and mortality globally. Compromised lung defences arising from immunosuppression, chronic respiratory conditions or more recently, concomitant viral or bacterial pulmonary infections are recognised risks factors for the development of pulmonary aspergillosis. In this review, we will summarise our current knowledge of the mechanistic basis of pulmonary aspergillosis with a focus on emerging at-risk populations.