Pseudomonas aeruginosa modulates neutrophil granule exocytosis in an in vitro model of airway infection

Immunol Cell Biol. 2022 Mar 23. doi: 10.1111/imcb.12547. Online ahead of print.

ABSTRACT

A population of neutrophils recruited into cystic fibrosis (CF) airways is associated with proteolytic lung damage, exhibiting high expression of primary granule exocytosis marker CD63 and reduced phagocytic receptor CD16. Causative factors for this population are unknown, limiting intervention. Here we present a laboratory model to characterise responses of differentiated airway epithelium and neutrophils following respiratory infection. Paediatric primary airway epithelial cells were cultured at air liquid interface (ALI), challenged individually or in combination with rhinovirus and Pseudomonas aeruginosa, then apically washed with medical saline to sample epithelial infection milieus. Cytokine multiplex analysis revealed epithelial antiviral signals including IP-10 and RANTES increased with exclusive rhinovirus infection but were diminished if P. aeruginosa was also present. Pro-inflammatory signals IL-1α and β were dominant in P. aeruginosa infection milieus. Infection washes were also applied to a published model of neutrophil transmigration into the airways. Neutrophils migrating into bacterial and viral-bacterial co-infection milieus exhibited the in vivo CF phenotype of increased CD63 expression and reduced CD16 expression, while neutrophils migrating into milieus of rhinovirus infected or uninfected cultures did not. Individually, bacterial products LPS and fMLF and isolated cytokine signals only partially activated this phenotype, suggesting additional soluble factors in the infection microenvironment trigger primary granule release. Findings identify P. aeruginosa as a trigger of acute airway inflammation and neutrophil primary granule exocytosis, underscoring potential roles of airway microbes in prompting this neutrophil subset. Further studies are required to characterise microbes implicated in primary granule release, and identify potential therapeutic targets.

PMID:35318736 | DOI:10.1111/imcb.12547

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