Possible link between cystic fibrosis specific lipid A adaptations by Pseudomonas aeruginosa and disease associated hyperinflammation.

• DOI: 10.4049/jimmunol.196.supp.65.23
• Publication Date: 2023-01-01T09:49:01Z
• Authors: Shuvasree SenGupta; Silvia M Uriarte; Robert K Ernst; Thomas C Mitchell
• Keywords: Neutrophilia; Neutrophil Extracellular Traps

Abstract Pseudomonas aeruginosa infection in cystic fibrosis (CF) lung disease causes airway neutrophilia and hyperinflammation without being cleared effectively. We evaluated the immunostimulatory activities of lipid A variants synthesized by P. (PA) exclusively CF patients to determine if they correlate with severity progression. One third PA isolates from late severe stage express a unique hepta–acylated A; hepta-1855 (m/z=1855) isoform. In primary cell cultures, we found that functioned as potent TLR4 agonist priming neutrophil respiratory burst stimulating strong chemokine response (interleukin-8 or IL-8) monocytes neutrophils. Hepta-1855 also had survival effect on However, it was less efficient inducing granule exocytosis triggering pro-inflammatory TNF-α monocytes. precursor hexa-1616, containing LPS mixtures, did not have direct inflammatory activity neutrophils but induced moderate IL-8 response. Together, our data suggest potential contribution associated excessive burden recruiting via promoting their maintenance through its effect. Being chemoattractant stimulus, may serve an accomplice hepta-1855. Moreover, relative inefficiency degranulation partly explain persistence spite dominated inflammation.