The mould Aspergillus fumigatus is the main causative agent of invasive pulmonary aspergillosis in immunocompromised patients. Infection starts with the inhalation of A. fumigatus conidia that germinate in the lung. Professional phagocytes like alveolar macrophages contribute to the efficient clearance of fungi from the lung by phagocytosis and degradation of conidia followed by release of chemokines and cytokines in order to trigger neutrophil migration at the site of infection. In the immunocompromized host, at least some conidia are able to evade macrophage degradation, resulting in germination and outgrowth of intracellularly residing spores. Therefore, conidia must be able to evade recognition and processing by phagocytes. The avirulent pksP mutant of A. fumigatus lacking the melanin layer present on wild-type conidia exhibited increased phagocytosis by macrophages apparently due to the loss of masking immunogenic glucan-structures. Furthermore, by analysing phagolysosome fusion and acidification we show that intracellular processing of pksP mutant conidia is drastically increased in comparison to wild-type conidia, suggesting that A. fumigatus conidia interfere with the endocytosis pathway, similar to obligate human pathogens like Legionella sp. or Mycobacterium sp.. The process by which wild-type conidia mediate endocytotic alterations seems to be connected to the surface structure of melanized conidia but is independent of the presence of a functional RodA-derived rodlet layer. Moreover, inhibition of phagolysosome acidification by macrophages is controlled by the fungal cAMP signaling pathway.
Full conference title:
26th Fungal Genetics Conference
- Fungal Genetics Conference 26th (2005)