Pseudomonas aeruginosa influences the inflammatory response of primary bronchial epithelial cells to rhinovirus infection

Endres, Adrian; Schubert, Ralf; Braubach, Peter; Jonigk, Danny; Hogardt, Michael; Boland, Helena; Rohde, Gernot; Bellinghausen, Carla

doi:10.1183/13993003.congress-2020.4343

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“…Exclusive viral infection elicited canonical antiviral signals, while responses to P. aeruginosa infection reflected an acute inflammatory response and were dominant over antiviral signals in co-infection with RV, despite high cytotoxicity following exclusive viral infection. This parallels findings where co-infection of RV with P. aeruginosa dampened viral-mediated IFN responses, IL-6 production and increased release of IL-1b and viral replication in AECs, [31][32][33] suggesting mechanisms by which P. aeruginosa modulates host responses to RV. Our results show significant reduction of IL-6, IFNassociated cytokines and high IL-1b release upon coinfection with P. aeruginosa; however, this did not lead to increases in RV titers.…”

Section: Discussionsupporting

confidence: 82%

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

et al. 2022

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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 characterize responses of differentiated airway epithelium and neutrophils following respiratory infection. Pediatric primary airway epithelial cells were cultured at the air–liquid interface, challenged individually or in combination with rhinovirus (RV) 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 RV infection but were diminished if P. aeruginosa was also present. Proinflammatory signals interleukin‐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 RV‐infected or uninfected cultures did not. Individually, bacterial products lipopolysaccharide and N‐formylmethionyl‐leucyl‐phenylalanine and isolated cytokine signals only partially activated this phenotype, suggesting that 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 characterize microbes implicated in primary granule release, and identify potential therapeutic targets.

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Section: Discussionsupporting

confidence: 82%