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Abstract
Aspergillus fumigatus is an environmental filamentous fungus that also acts as an opportunistic pathogen able to cause a variety of symptoms, from an allergic response to a life-threatening disseminated fungal infection. The infectious agents are inhaled conidia whose first point of contact is most likely to be an airway epithelial cell (AEC). The interaction between epithelial cells and conidia is multifaceted and complex, and has implications for later steps in pathogenesis. Increasing evidence has demonstrated a key role for the airway epithelium in the response to respiratory pathogens, particularly at early stages of infection; therefore, elucidating the early stages of interaction of conidia with AECs is essential to understand the establishment of infection in cohorts of at-risk patients. Here, we present a comprehensive review of the early interactions between A. fumigatus and AECs, including bronchial and alveolar epithelial cells. We describe mechanisms of adhesion, internalization of conidia by AECs, the immune response of AECs, as well as the role of fungal virulence factors, and patterns of fungal gene expression characteristic of early infection. A clear understanding of the mechanisms involved in the early establishment of infection by A. fumigatus could point to novel targets for therapy and prophylaxis.
Highlights
Aspergillus fumigatus is a saprotrophic filamentous fungus that plays an important environmental role in the carbon and nitrogen cycles through the decomposition of organic matter
Unlike phospholipase D (PLD), the change in the ratio of phosphorylated cofilin-1 to unphosphorylated cofilin-1 was not mediated by exposure to β-glucan, implying that the inactivation of cofilin was mediated through a different signaling event (Bao et al, 2015). The involvement of both molecules appears to be essential for efficient internalization as silencing of the expression of either PLD or cofilin-1 resulted in a decreased conidial uptake (Han et al, 2011; Jia et al, 2014; Bao et al, 2015) (Figure 3)
It is interesting to note that the results of Amin et al (2014) were obtained using a uracil auxotrophic strain of A. fumigatus; this strain cannot germinate within the endosomal system
Summary
Aspergillus fumigatus is a saprotrophic filamentous fungus that plays an important environmental role in the carbon and nitrogen cycles through the decomposition of organic matter. A. fumigatus is not the most prevalent species of Aspergillus, it is one of the most ubiquitous, found in the soil of vastly different environments from the northern tundra to the tropics (Pringle et al, 2005). A cycle of sexual reproduction has been characterized in this species (O’Gorman et al, 2009); the overall genetic variation between different isolates is comparatively low (Rydholm et al, 2006). A. fumigatus is primarily spread through the release of conidia; these are small, asexually produced haploid spores approximately 2–3 μm in diameter that can be disseminated by air currents (Mullins et al, 1976)
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