Fine Particulate Matter (PM2.5) Promotes CD146 Expression in Alveolar Epithelial Cells and Cryptococcus neoformans Pulmonary Infection

Abstract

Air pollution is a leading cause of increasing infectious lung diseases. Pulmonary cryptococcosis is a fatal fungal pneumonia in acquired immunodeficiency syndrome patients. In some cases, the pathogen Cryptococcus neoformans also develops dormant nodules in immunocompetent individuals. In the present study, we demonstrated that fine particulate matter (PM2.5) increased CD146 expression in alveolar epithelial cells and promoted C. neoformans pulmonary infection. Aryl hydrocarbon receptor (AhR) signaling was required for increased expression of CD146 in epithelial cells treated with PM2.5. In a murine model of pulmonary infection, PM2.5 promoted fungal infection, and CD146 deficiency decreased the fugal burden of C. neoformans. Our study may highlight the importance of air pollution to lung mycosis and CD146 as a target for preventing infectious lung diseases.

Contribution of Particulates to Airborne Disease Transmission and Severity: A Review

“…Penicillium , which is known for many species that produce mycotoxins, and yeasts were positively correlated with PMs in the investigation among five species of fungi detected; the remaining Alternaria , Aspergillus , and Cladosporium showed low correlations with PMs. Additionally, although there has been no analysis on the relationship between Cryptococcus infection and PM concentration in the air, it has been confirmed that PM 2.5 promotes the infection by enhancing the adhesion of fungi to alveolar epithelial cells when in the lung …”

“…Additionally, although there has been no analysis on the relationship between Cryptococcus infection and PM concentration in the air, it has been confirmed that PM 2.5 promotes the infection by enhancing the adhesion of fungi to alveolar epithelial cells when in the lung. 148 The time difference between the outbreak of fungal disease and the increase in airborne PM concentration tends to be longer than other microorganisms. [12][13][14][134][135][136]138 The time taken from the time of initial exposure to the fungus to the onset of the disease varies depending on the patient, and the degree of exposure and the activity of the fungus in the air may also differ.…”

The CD146-HIF-1α axis regulates epithelial cell migration and alveolar maturation in a mouse model of bronchopulmonary dysplasia

“…As an adhesion molecule, CD146 regulates the migration of monocytes 6 and endothelial cells 7 , 8 . In pulmonary epithelial cells, CD146 promotes the adherence of viruses 9 , bacteria 10 , and fungi 11 to the pulmonary epithelium. However, the roles of CD146 in the migration of alveolar epithelial cells and the maturation of alveoli in the development of BPD are largely elusive.…”