tThrough the action of the type three secretion system (T3SS) Shigella flexneri delivers several effectorsinto host cells to promote cellular invasion, multiplication and to exploit host-cell signaling pathways tomodulate the host innate immune response. Although much progress has been made in the understandingof many type III effectors, the molecular and cellular mechanism of the OspB effector is still poorlycharacterized. In this study we present new evidence that better elucidates the role of OspB as pro-inflammatory factor at very early stages of infection. Indeed, we demonstrate that, during the first hourof infection, OspB is required for full activation of ERK1/2 and p38 MAPKs and the cytosolic phospholipaseA2(cPLA2). Activation of cPLA2ultimately leads to the production and secretion of PMN chemoattractantmetabolite(s) uncoupled with release of IL-8. Moreover, we also present evidence that OspB is requiredfor the development of the full and promptly inflammatory reaction characteristic of S. flexneri wild-type infection in vivo. Based on OspB and OspF similarity (both effectors share similar transcriptionregulation, temporal secretion into host cells and nuclear localization) we hypothesized that OspB andOspF effectors may form a pair aimed at modulating the host cell response throughout the infectionprocess, with opposite effects. A model is presented to illustrate how OspB activity would promote S.flexneri invasion and bacterial dissemination at early critical phases of infection.

The Shigella flexneri OspB effector: an early immunomodulator

NICOLETTI, Mauro
2015

Abstract

tThrough the action of the type three secretion system (T3SS) Shigella flexneri delivers several effectorsinto host cells to promote cellular invasion, multiplication and to exploit host-cell signaling pathways tomodulate the host innate immune response. Although much progress has been made in the understandingof many type III effectors, the molecular and cellular mechanism of the OspB effector is still poorlycharacterized. In this study we present new evidence that better elucidates the role of OspB as pro-inflammatory factor at very early stages of infection. Indeed, we demonstrate that, during the first hourof infection, OspB is required for full activation of ERK1/2 and p38 MAPKs and the cytosolic phospholipaseA2(cPLA2). Activation of cPLA2ultimately leads to the production and secretion of PMN chemoattractantmetabolite(s) uncoupled with release of IL-8. Moreover, we also present evidence that OspB is requiredfor the development of the full and promptly inflammatory reaction characteristic of S. flexneri wild-type infection in vivo. Based on OspB and OspF similarity (both effectors share similar transcriptionregulation, temporal secretion into host cells and nuclear localization) we hypothesized that OspB andOspF effectors may form a pair aimed at modulating the host cell response throughout the infectionprocess, with opposite effects. A model is presented to illustrate how OspB activity would promote S.flexneri invasion and bacterial dissemination at early critical phases of infection.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11564/599917
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