Interactions of Aspergillus fumigatus Conidia with Airway Epithelial Cells: A Critical Review

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.

Keywords: Aspergillus fumigatus; airway epithelial cell; aspergillosis; conidia; host–pathogen interactions; immunity; virulence.

FIGURE 1

The structures of the lung epithelium. The basic structure and primary cell types of the bronchial (A) and alveolar (B) epithelia.

FIGURE 2

Timeline of the events of the early interaction. The initiation of different stages of interaction of Aspergillus fumigatus with host lung are indicated on a relative timeline. The events shown in the figure have been demonstrated to occur within the first 16 h of contact.

FIGURE 3

Model of internalization of A. fumigatus conidia by airway epithelial cells. Once conidia swell, β-glucan in the conidial cell wall is recognized by dectin-1, activating PLD-1 and PLD-2 (isoforms of phospholipase D) and promoting actin polymerization. Another, as yet uncharacterized signal results in the phosphorylation of cofilin-1, causing it to release actin. Conidia are then internalized through actin and microtubule polymerization and phagocytosis. Upon internalization, they are trafficked through the endosomal system where they are degraded and cleared from the host or alternatively, small numbers may persist, germinate and escape.