Bronchial Epithelial Cells on the Front Line to Fight Lung Infection-Causing Aspergillus fumigatus

Abstract

Aspergillus fumigatus is an environmental filamentous fungus that can be pathogenic for humans, wherein it is responsible for a large variety of clinical forms ranging from allergic diseases to life-threatening disseminated infections. The contamination occurs by inhalation of conidia present in the air, and the first encounter of this fungus in the human host is most likely with the bronchial epithelial cells. Although alveolar macrophages have been widely studied in the Aspergillus-lung interaction, increasing evidence suggests that bronchial epithelium plays a key role in responding to the fungus. This review focuses on the innate immune response of the bronchial epithelial cells against A. fumigatus, the predominant pathogenic species. We have also detailed the molecular interactants and the effects of the different modes of interaction between these cells and the fungus.

Characterisation of Aspergillus fumigatus Endocytic Trafficking within Airway Epithelial Cells Using High-Resolution Automated Quantitative Confocal Microscopy

“…Live-cell confocal microscopy was used to quantitatively compare phagolysosome dynamics, during A. fumigatus spore internalization, within bronchial (16HBE) and alveolar (A549) epithelial cell lines. These cell lines represent the epithelial lining of the upper and lower airways, both critical in the pathophysiology of aspergillosis [49,50].…”

Airway Epithelial Innate Immunity

“…Like helminth infestations, fungal infections of the airways also prominently evoke Type 2 epithelial responses. Historically, this was first recognized in allergic bronchopulmonary aspergillosis (ABPA), but recently, infection by various other fungi has been found to be a frequent driver of allergic asthma, and Type 2 epithelial responses have been demonstrated to be fungistatic, cementing the relationship between fungal infection and Type 2 responses (Millien et al, 2013;Bigot et al, 2020). Mechanisms that underlie Type 2 epithelial immunity and their therapeutic manipulation are the focus of this section.…”

“…Specifically, lumenal mucus traps larvae in the airway lumen, preventing the completion of the parasite life cycle of migration to the gut. Similarly, chitinases and chitinase-like proteins promote resistance to both parasites and fungi, but can also contribute to the pathophysiology of asthma and other airway diseases (Bigot et al, 2020;Przysucha et al, 2020). The roles of multiple other molecules involved in Type 2 epithelial responses have a similar two-sided character, participating both in resistance to helminths and fungi and in the pathogenesis of non-infectious airway diseases (Hammad and Lambrecht, 2021).…”

Cytokine and Chemokine Responses in Invasive Aspergillosis Following Hematopoietic Stem Cell Transplantation: Past Evidence for Future Therapy of Aspergillosis

“…The cellular response of the airway bronchial epithelial cells to Aspergillus is the first layer of protection against the pathogen. The major roles of bronchial epithelial cells include enhancing recruitment of macrophages and neutrophils, increasing the release of proinflammatory cytokines and chemokines, and activating and skewing T-cell subsets [56]. The engulfment of conidia and/or hyphae by alveolar macrophages leads to the release of numerous cytokines and chemokines that further enhance the recruitment of innate effector cells including macrophages and DCs [57].…”