Aspergillus fumigatus is an environmental filamentous fungus that may act as an opportunistic pathogen causing a variety of diseases, including asthma or allergic bronchopulmonary aspergillosis, and infection, ranging from asymptomatic colonization to invasive pulmonary form, especially in immunocompromised patients. This fungus is characterized by different morphotypes including conidia which are the infective propagules able to germinate into hyphae. Due to their small size (2–3 µm), conidia released in the air can reach the lower respiratory tract. The objective of this study was to characterize the interactions between conidia and bronchial epithelial cells. To this end, we studied the role of bronchial epithelial cells, i.e., the BEAS-2B cell line and human primary cells, in conidial germination of a laboratory strain and three clinical strains of A. fumigatus. Microscopic observations and galactomannan measurements demonstrated that contact between epithelial cells and conidia leads to the inhibition of conidia germination. We demonstrated that this fungistatic process is not associated with the release of any soluble components nor internalization by the epithelial cells. We highlight that this antifungal process involves the phosphoinositide 3-kinase pathway on the host cellular side and the lectin FleA on the fungal side. Collectively, our results show that bronchial epithelial cells attenuate fungal virulence by inhibiting germination of extracellular conidia, thus preventing the morphological change from conidia to filaments, which is responsible for tissue invasion.

Objectives To examine the incidence, predictors and outcomes associated with severe gastrointestinal (GI) disease in a large inception SSc cohort. Methods SSc subjects with <2 years of disease duration were identified from two multicentre cohorts. Severe GI disease was defined as: malabsorption, hyperalimentation, pseudo-obstruction and/or ⩾10% weight loss in association with the use of antibiotics for bacterial overgrowth or oesophageal stricture. Kaplan–Meier, multivariate logistic regression and Cox proportional hazard analyses were performed to determine the cumulative incidence rate, independent clinical correlates and mortality rate associated with severe GI disease. A longitudinal mixed model was used to assess the impact of severe GI disease on the Short Form Health Survey. Results In this inception SSc cohort, the probability of developing severe GI disease was estimated at 9.1% at 2 years and 16.0% at 4 years. In multivariate analysis, severe GI disease was associated with inflammatory myositis (odds ratio 4.68, 95% CI 1.65, 13.24), telangiectasias (odds ratio 2.45, 95% CI 1.19, 5.04) and modified Rodnan skin score (odds ratio 1.03, 95% CI 1.01, 1.07). Severe GI disease was associated with a >2-fold increase in the risk of death (hazard ratio 2.27, 95% CI 1.27, 4.09) and worse health-related quality of life [Short Form Health Survey physical (β = −2.37, P = 0.02) and mental (β = −2.86, P = 0.01) component summary scores]. Conclusion Severe GI disease is common in early SSc and is associated with significant morbidity and increased mortality. More research is needed to understand, prevent and mitigate severe GI disease in SSc.