Interaction of Aspergillus with alveolar Type II cells and phagocytes

Abstract

Aspergillus species are worldwide distributed fungi and abundant in nature. Aspergilli are mainly saprotrophic obtaining nutrients by degrading dead organic material in particular that of plants. Currently, around 837 species have been reported. Due to the broad range of compound secreted by Aspergillus, multiple species have been widely exploited in industry for the production of enzymes, secondary metabolites and organic acids. Only few Aspergili can cause human, animal and plant diseases. Human aspergillosis is ranked as the second most common fungal lung infection in hospitals representing a threat for immunocompromised individuals. Conidia are the infectious propagules which can easily disperse by air and water droplets. Aspergillus fumigatus is recognized as the main causative agent of invasive aspergillosis. This disease remain highly lethal, depending in the immune status of the patient mortality rate can rise up to 50 %. The reason why A. fumigatus is such a prominent opportunistic pathogen in comparison to other Aspergillus species is not yet well understood. The PhD candidate Natalia Escobar has studied the interaction of Aspergillus species using an in vitro model of type II lung epithelial cells. In this study, she followed conidia from a non-pathogenic Aspergillus (A. niger) and A. fumigatus during three main steps for the initiation of the infection: adhesion, internalization, and germination. Striking differences in internalization and germination were found. A. fumigatus spores internalized more efficiently and germination was strongly delayed in the presence of lung epithelial cells in comparison with A. niger. Analysis of gene expression revealed that both species respond different when exposed to lung epithelial cells and also evoke different gene expression profiles in the host. Furthermore, culture media of several Aspergillus species were obtained and exposed to human immune cells (i.e. neutrophils, monocytes, and lymphocytes) in order to screen for secreted immume-modulating compounds that bind to cellular receptors. Heat stable moderately hydrophobic molecules ≤ 3KDa were found to bind to human cellular receptors involved in recognition and activation of the immune system.