Poly-N-acetyl glucosamine expression in Staphylococcus epidermidis biofilm cells affects the immune response and promotes tissue pathology in infected hosts
| Autor: | Ferreirinha, Pedro, Pérez-Cabezas, Begoña, Correia, Alexandra, Miyazawa, Bruna, Carvalhais, Virgínia Maria Dinis, França, Ângela Maria Oliveira Sousa, Faustinho, Augusto, Cordeiro-da-Silva, Anabela, Teixeira, Luzia, Pier, Geral, Cerca, Nuno, Vilanova, Manuel |
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| Přispěvatelé: | Universidade do Minho |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
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| Popis: | Staphylococcus epidermidis is a biofilm - forming bacterium and a leading etiological agent of nosocomial infections. The ability to establish biofilms on indwelling medical devices is a key virulence factor for this bacterium. Still, the influence of poly - N - acetyl glucosamine (PNAG), the major component of the extracellular biofilm matrix, in the host immune response has been scarcely studied. Here, t h is influence was assessed in mice challenged i.p. with PNAG - p roducing (WT) and isogenic - mutant lacking PNAG (M10) bacteria grown in biofilm - inducing conditions. Faster bacterial clearance was observed in the mice infected with WT bacteria than in M10 - infected counterparts , which w as accompanied by earlier neutrophil recruitment and higher IL - 6 production. Interestingly, in the WT - infected mice, but not in those infected with M10 , elevated serum IL - 10 was detected . To further study the effe ct of PNAG in the immune response, mice were primed with WT or M10 biofilm bacteria and subsequently infected with WT biofilm - released cells. WT - primed mice presented a higher frequency of splenic IFN - γ + and IL - 17 + CD4 + T cells, and more severe liver patho logy than M10 - primed counterparts. Nevertheless, T reg cells obtained from the WT - primed mice presented a higher suppressive function than those obtained from M10 - primed mice. This effect was abrogated when IL - 10 - deficient mice were similarly primed and infected indicating that PNAG promotes the differentiati on of highly suppressive T reg cells by a mechanism dependent on IL - 10. Altogether, these results provide evidence help ing explain ing the coexistence of inflammation and bacterial persistence often observed in biofilm - originated S. epidermidis infections FCT and COMPETE grants PTDC/BIA-MIC/113450/2009 and FCOMP-01-0124-FEDER-14309. PF, AC, LT and VC were supported by FCT grants SFRH/BD/76900/2011, SFRH/BPD/91623/2012, IF/01241/2014, SFRH/BD/78235/2011 |
| Databáze: | OpenAIRE |
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