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

Forskningsoutput: KonferensbidragPoster

Abstract

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<0.001) were observed with type II bronchial alveolar epithelial cells (A549) after stimulation with EVs. In conclusion, elevated vitronectin concentrations were found in BALF from patients with pneumonia and in healthy volunteers after pulmonary endotoxin instillation. Cellular experiments confirmed vitronectin production upon EV stimulation in vitro. Bacteria captured vitronectin from BALF on their surface to evade lysis by complement in serum. Hence, vitronectin is produced by epithelial cells upon bacterial infection and utilized by respiratory pathogens to persist in the respiratory tract.

Detaljer

Författare
Enheter & grupper
Externa organisationer
  • Karolinska Institute
  • Sahlgrenska Academy
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Mikrobiologi inom det medicinska området
Originalspråkengelska
SidorP132
StatusPublished - 2017 sep 5
PublikationskategoriForskning
Peer review utfördJa
Evenemang16th International Conference on Pseudomonas - Liverpool, Storbritannien
Varaktighet: 2017 sep 52017 sep 9

Konferens

Konferens16th International Conference on Pseudomonas
LandStorbritannien
OrtLiverpool
Period2017/09/052017/09/09

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