Vitronectin is produced in the lung upon infection by respiratory pathogens, and is utilized to evade the innate immunity

Bacterial extracellular vesicles (EVs) are shed during growth by the respiratory pathogens Pseudomonas aeruginosa and Haemophilus influenzae. Vesicles trigger release of antimicrobial compounds and proteins of the complement, which are partly regulated by vitronectin. We hypothesized that vitronectin is elevated in the lungs during pneumonia, that respiratory epithelial cells produce vitronectin upon bacterial stimulation and that vitronectin is utilized by bacteria for increased virulence. Vitronectin-concentrations were measured by ELISA in bronchoalveolar lavage fluid (BALF) from patients with pneumonia (n=8) and from healthy volunteers (n=13) with or without pulmonary endotoxin instillation. Elevated vitronectin concentrations were found in BALF collected during pneumonia compared to healthy individuals (p=0.0063) and in endotoxin-challenged pulmonary segments compared to control segments (after 12h: p=0.031; 48h: p=0.016). Flow cytometry revealed that bacteria captured vitronectin from BALF onto their surface and subsequently became less sensitive to killing by serum compared to controls (P. aeruginosa p=0.016, H. influenzae p=0.011). Increased levels of VTN mRNA after one hour (p=0.022) and increased surface bound vitronectin after 24h (p