Lung epithelium: barrier immunity to inhaled fungi and driver of fungal-associated allergic asthma

Abstract

Fungi are ubiquitous in the environment. The epithelium that lines our airways is the first point of contact with the frequent encounter of inhaled fungi. Consequently, the lung epithelium has evolved behaviors that instruct the earliest immune events to resist fungal penetration. Although the epithelium efficiently assists in immunity to invasive fungi, it also can be inappropriately triggered, to the detriment of the host, by normally innocuous fungi or fungal components. Thus, there is a tipping point of protective immunity against fungal pathogens versus inflammatory disease caused by an exuberant immune response to harmless fungal antigens. This review will discuss several aspects of barrier immunity to pulmonary fungal infection, as well as situations where fungal exposure leads to allergic asthma.

Helper T‐cell responses and pulmonary fungal infections

“…The lungs represent a massive environment‐exposed surface in the body, which is challenged with microbes and microbial products with every breath . Fungi represent a medically important class of pathogenic microbes, and 4–11% of the fine‐particle mass inhaled into the lungs contains fungal spores .…”

“…Fungi represent a medically important class of pathogenic microbes, and 4–11% of the fine‐particle mass inhaled into the lungs contains fungal spores . To preserve epithelial integrity and prevent colonization by infectious organisms including fungi, the host has developed several immunological mechanisms in the lungs . Epithelial cells provide barrier immunity, preventing inhaled particles access to deeper tissues and vasculature, while mucus and antimicrobial peptides further deter colonization .…”

“…To preserve epithelial integrity and prevent colonization by infectious organisms including fungi, the host has developed several immunological mechanisms in the lungs . Epithelial cells provide barrier immunity, preventing inhaled particles access to deeper tissues and vasculature, while mucus and antimicrobial peptides further deter colonization . Resident alveolar macrophages remove debris from the lungs, maintaining clear airways and preventing the establishment of infection.…”

The Human Lung Mycobiome in Chronic Respiratory Disease: Limitations of Methods and Our Current Understanding

“…However, in some patients with a long-term respiratory condition such as asthma, COPD, bronchitis or cystic fibrosis (CF), spores can evade the lung immune response and germinate to persist in the airways [3]. Changes in nutrient composition in the lungs from patients with chronic respiratory infections [4], impaired mucociliary clearance or increased mucus secretion [4,5] might be responsible for increased fungal burdens in these patients. Additionally, fungal persistence in the lungs from patients with long-term respiratory diseases has been associated with worse disease outcome and increases the risk for the development of lethal fungal diseases such as chronic pulmonary aspergillosis [6].…”

“…This suggests that approximately one fungal spore is deposited per 100 cm 2 region of the lung per day as a result of inhalation [8]. Ungerminated spores are likely to be rapidly cleared by the mucociliary escalator and by resident macrophages, and therefore, the levels of fungal spores in a healthy lung are extremely low [5]. Colonisation begins when spores germinate to form a stable locus of growth [9], and after 24-48 h growth a single uninucleate spore or yeast cell can form a mycelium or dispersed yeast colony containing more than 100 nuclei [10].…”