Poly-N-acetylglucosamine production by Staphylococcus epidermidis cells increases their in vivo proinflammatory effect

Poly-N-acetyl glucosamine (PNAG) is a major component of Staphylococcus epidermidis biofilms extracellular matrix. However, it is not yet clear how this polysaccharide impacts the host immune response and infection-associated pathology. Faster neutrophil recruitment and bacterial clearance was observed in mice challenged intraperitoneally with S. epidermidis biofilm cells of the PNAG-producing 9142 strain than in mice similarly challenged with the isogenic PNAG-defective M10 mutant. Moreover, intraperitoneal priming with 9142 cells exacerbated liver inflammatory pathology induced by a subsequent intravenous S. epidermidis challenge when compared to priming with M10 cells. The 9142-primed mice had elevated splenic CD4+ T cells producing IFN- and IL-17A, indicating that PNAG promoted cell-mediated immunity. Curiously, despite having more marked liver tissue pathology, 9142-primed mice also had splenic T regulatory cells with increased suppressive activity compared with the M10-primed counterparts. By showing that PNAG production by S. epidermidis biofilm cells exacerbates host inflammatory pathology these results altogether suggest that this polysaccharide contributes for the clinical features associated to biofilm originated infections. Fundação para a Ciência e a Tecnologia (FCT) and COMPETE [grant numbers PTDC/BIA-MIC/113450/2009, FCOMP-01-0124-FEDER-014309, FCOMP‐01‐0124‐FEDER‐022718, FCT PEst‐C/SAU/LA0002/2011, NORTE-01-0145-FEDER-000012]. The following authors received individual FCT fellowships: PF (SFRH/BD/76900/2011), AC (SFRH/BPD/91623/2012), VC (SFRH/BD/78235/2011), AF (SFRH/BPD/99961/2014). LT was supported by Fundo Social Europeu and Programa Operacional Potencial Humano through FCT Investigator [grant number IF/01241/2014].