Aspergillus-Associated Airway Disease, Inflammation, and the Innate Immune Response

Abstract

Aspergillus moulds exist ubiquitously as spores that are inhaled in large numbers daily. Whilst most are removed by anatomical barriers, disease may occur in certain circumstances. Depending on the underlying state of the human immune system, clinical consequences can ensue ranging from an excessive immune response during allergic bronchopulmonary aspergillosis to the formation of an aspergilloma in the immunocompetent state. The severest infections occur in those who are immunocompromised where invasive pulmonary aspergillosis results in high mortality rates. The diagnosis of Aspergillus-associated pulmonary disease is based on clinical, radiological, and immunological testing. An understanding of the innate and inflammatory consequences of exposure to Aspergillus species is critical in accounting for disease manifestations and preventing sequelae. The major components of the innate immune system involved in recognition and removal of the fungus include phagocytosis, antimicrobial peptide production, and recognition by pattern recognition receptors. The cytokine response is also critical facilitating cell-to-cell communication and promoting the initiation, maintenance, and resolution of the host response. In the following review, we discuss the above areas with a focus on the innate and inflammatory response to airway Aspergillus exposure and how these responses may be modulated for therapeutic benefit.

The basophil surface marker CD203c identifies Aspergillus species sensitization in patients with cystic fibrosis

“…4 The fungus is associated with a range of manifestations in CF, most commonly allergic bronchopulmonary aspergillosis (ABPA) and less commonly, aspergillomas and invasive pulmonary aspergillosis. [5][6][7] ABPA affects between 2%-15% of patients with CF (PWCF) and recurrent episodes impact pulmonary function. 1, [8][9][10][11] It manifests as an allergic, hypersensitive, Th2 CD4 + cell-driven response to Af and the diagnosis of ABPA in CF is particularly challenging due to overlapping clinical, immunological and radiological features that are similar to those of a pulmonary exacerbation.…”

Airway centered invasive pulmonary aspergillosis in an immunocompetent patient: case report and literature review

“…Invasive pulmonary aspergillosis, including the angioinvasive and airway centered invasive type, typically occurs in exclusively immunocompromised patients, especially those with neutropenia and those with HIV infection, after solid organ transplantation, who receive immunosuppressive or steroid therapy for chronic granulomatous disease (2,4,7,8).…”

Pulmonary solid tumor with coexisting pulmonary aspergillosis: case reports and literature review

“…More than 200 species of Aspergillus have been described, approximately 10% of which are pathogenic to humans (12). The most frequent causative agents of pulmonary aspergillosis are A. fumigatus, A. flavus and A. niger (13).…”

“…Aspergillus produces a large number of small (2-5 μm), dry, hydrophobic conidia. In fact, normal air contains a concentration range of 1-100 spores/m 3 , which are easily inhaled, can reach the lower respiratory tract and penetrate deeply into the alveoli (11,12). Resultant disease depends on the host's immune state, ranging from commensalism or symbiosis to a pathogenic phase that causes common clinical syndromes or fatal infections (14).…”