Microbial interaction: Prevotella spp. reduce P.aeruginosa induced inflammation in Cystic Fibrosis bronchial epithelial cells

Background: In Cystic Fibrosis (CF) airways, mutations in the Cystic Fibrosis Transmembrane Regulator (CFTR) lead to dehydrated, thick mucus which promotes the establishment of persistent polymicrobial infections and drives chronic airways inflammation. This also predisposes the airways to further infections, a vicious, self-perpetuating cycle causing lung damage and progressive lung function decline. The airways are a poly-microbial environment, containing both aerobic and anaerobic bacterial species. Pseudomonas aeruginosa (P.aeruginosa) infections contribute to the excessive inflammatory response in CF, but the role of anaerobic Prevotella spp., frequently found in CF airways, is not known.Materials: We assessed innate immune signalling in CF airway epithelial cells in response to clinical strains of P.histicola, P.nigresens and P.aeruginosa. CFBE41o- cells were infected with P.aeruginosa (MOI 100, 2h) followed by infection with P.histicola or P.nigrescens (MOI 100, 2h). Cells were incubated under anaerobic conditions for the duration of the experiments.Results: Our study shows that P.histicola and P.nigresens can reduce the growth of P.aeruginosa and dampen the inflammatory response in airway epithelial cells. We specifically illustrate that the presence of Prevotella spp. reduces Toll-like-receptor (TLR)-4, MAPK, NF-kB(p65) signalling and cytokine release (Interleukin (IL)-6, IL-8) in mixed infections. Conclusion: Our work, for the first time, strongly indicates a relationship between P. aeruginosa and anaerobe Prevotella spp. The observed modified NF-kB and MAPK signalling provides some mechanisms of this interaction that could offer a novel therapeutic approach to combat chronic P.aeruginosa infection in people with CF.