| Autor: |
Bebien, Magali, Hensler, Mary E., Davanture, Suzel, Li-Chung Hsu, Karin, Michael, Park, Jin Mo, Alexopoulou, Lena, Liu, George Y., Nizet, Victor, Lawrence, Toby |
| Předmět: |
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| Zdroj: |
PLoS Pathogens; Jul2012, Vol. 8 Issue 7, Special section p1-11, 11p, 2 Diagrams, 5 Graphs |
| Abstrakt: |
Group B Streptococcus (GBS) is a leading cause of invasive bacterial infections in human newborns and immunecompromised adults. The pore-forming toxin (PFT) β hemolysin/cytolysin (βh/c) is a major virulence factor for GBS, which is generally attributed to its cytolytic functions. Here we show βh/c has immunomodulatory properties on macrophages at sub-lytic concentrations. βh/c-mediated activation of p38 MAPK drives expression of the anti-inflammatory and immunosuppressive cytokine IL-10, and inhibits both IL-12 and NOS2 expression in GBS-infected macrophages, which are critical factors in host defense. Isogenic mutant bacteria lacking βh/c fail to activate p38-mediated IL-10 production in macrophages and promote increased IL-12 and NOS2 expression. Furthermore, targeted deletion of p38 in macrophages increases resistance to invasive GBS infection in mice, associated with impaired IL-10 induction and increased IL-12 production in vivo. These data suggest p38 MAPK activation by βh/c contributes to evasion of host defense through induction of IL-10 expression and inhibition of macrophage activation, a new mechanism of action for a PFT and a novel anti-inflammatory role for p38 in the pathogenesis of invasive bacterial infection. Our studies suggest p38 MAPK may represent a new therapeutic target to blunt virulence and improve clinical outcome of invasive GBS infection. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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