Interaction of the pathogenic mold Aspergillus fumigatus with lung epithelial cells

Abstract

Aspergillus fumigatus is an opportunistic environmental mold that can cause severe allergic responses in atopic individuals and poses a life-threatening risk for severely immunocompromised patients. Infection is caused by inhalation of fungal spores (conidia) into the lungs. The initial point of contact between the fungus and the host is a monolayer of lung epithelial cells. Understanding how these cells react to fungal contact is crucial to elucidating the pathobiology of Aspergillus-related disease states. The experimental systems, both in vitro and in vivo, used to study these interactions, are described. Distinction is made between bronchial and alveolar epithelial cells. The experimental findings suggest that lung epithelial cells are more than just “innocent bystanders” or a purely physical barrier against infection. They can be better described as an active extension of our innate immune system, operating as a surveillance mechanism that can specifically identify fungal spores and activate an offensive response to block infection. This response includes the internalization of adherent conidia and the release of cytokines, antimicrobial peptides, and reactive oxygen species. In the case of allergy, lung epithelial cells can dampen an over-reactive immune response by releasing anti-inflammatory compounds such as kinurenine. This review summarizes our current knowledge regarding the interaction of A. fumigatus with lung epithelial cells. A better understanding of the interactions between A. fumigatus and lung epithelial cells has therapeutic implications, as stimulation or inhibition of the epithelial response may alter disease outcome.

The mtfA Transcription Factor Gene Controls Morphogenesis, Gliotoxin Production, and Virulence in the Opportunistic Human Pathogen Aspergillus fumigatus

“…Inhalation of A. fumigatus conidia can cause allergic bronchopulmonary aspergillosis, an allergic response to the spores that occurs in hypersensitive patients (1,2). In immunodepressed patients A. fumigatus is the leading causative agent of invasive aspergillosis (IA).…”

“…The first point of contact is with the bronchial epithelial cells (1). These cells have dectin-1 receptors that can recognize the ␤-1,3-glucan on the cell surfaces of conidia (1,13,14), activating the production of reactive oxygen species (ROS) and of antimicrobial peptides and cytokines as part of the initial immune response. In healthy individuals, conidia that are able to evade mucociliary clearance are quickly removed by either alveolar macrophages or epithelial cells via phagocytosis.…”

“…The small size (2.5 to 3.0 m) of the asexual spores, called conidia, allows them to reach the lung alveoli (12). The first point of contact is with the bronchial epithelial cells (1). These cells have dectin-1 receptors that can recognize the ␤-1,3-glucan on the cell surfaces of conidia (1,13,14), activating the production of reactive oxygen species (ROS) and of antimicrobial peptides and cytokines as part of the initial immune response.…”

Hydrogen peroxide-induced secondary necrosis in conidia of Aspergillus fumigatus

“…Both of these types of immune cells are able to generate reactive oxygen species (ROS) (Hamann et al 2008); it is a matter of debate whether ROS contribute to inactivation of conidia or act as signaling molecules (Giorgio et al 2007). In hypersensitive patients, the inhalation of these bioparticles is associated with allergic diseases, such as asthma, allergic bronchopulmonary aspergillosis, aller-gic sinusitis, and alveolitis (Osherov 2012). However, the situation changes in immunocompromised patients, such as those with hematological malignancies or with solid-organ and hematopoietic stem cell transplants; in patients on prolonged corticosteroid therapy; and in individuals with genetic immunodeficiencies (e.g., chronic granulomatous disease) or infected with human immunodeficiency virus.…”

“…However, the situation changes in immunocompromised patients, such as those with hematological malignancies or with solid-organ and hematopoietic stem cell transplants; in patients on prolonged corticosteroid therapy; and in individuals with genetic immunodeficiencies (e.g., chronic granulomatous disease) or infected with human immunodeficiency virus. In these patients, the highly resistant conidial structures can evade macrophage recognition and develop into massive hyphal aggregates (responsible for the outset of invasive disease) and trigger inflammatory responses (Osherov 2012). Invasive aspergillosis is perhaps the most devastating of Aspergillus-related illnesses (Dagenais and Keller 2009).…”