title: The Shigella flexneri OspB effector: an early immunomodulator.
abstract: Through the action of the type three secretion system (T3SS) Shigella flexneri delivers several effectors into host cells to promote cellular invasion, multiplication and to exploit host-cell signaling pathways to modulate the host innate immune response. Although much progress has been made in the understanding of many type III effectors, the molecular and cellular mechanism of the OspB effector is still poorly characterized. 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 hour of infection, OspB is required for full activation of ERK1/2 and p38 MAPKs and the cytosolic phospholipase A(2) (cPLA(2)). Activation of cPLA(2) ultimately leads to the production and secretion of PMN chemoattractant metabolite(s) uncoupled with release of IL-8. Moreover, we also present evidence that OspB is required for 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 transcription regulation, temporal secretion into host cells and nuclear localization) we hypothesized that OspB and OspF effectors may form a pair aimed at modulating the host cell response throughout the infection process, 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.
authors.affiliation: Dipartimento di Scienze di Sanità Pubblica e Malattie Infettive, "Sapienza" Università di Roma, 00185 Rome, Italy. Electronic address: cecilia.ambrosi@uniroma1.it.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Ambrosi
authors.affiliation: Dipartimento di Scienze di Sanità Pubblica e Malattie Infettive, "Sapienza" Università di Roma, 00185 Rome, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Pompili
authors.affiliation: Dipartimento di Scienze Sperimentali e Cliniche, Università "G. D'Annunzio", 66100 Chieti, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Scribano
authors.affiliation: San Raffaele, Istituto di Ricovero e Cura a Carattere Scientifico IRCCS, Università Telematica San Raffaele Rome, Italy.
authors.forename: Dolores
authors.initials: D
authors.lastname: Limongi
authors.affiliation: Laboratorio di Microbiologia Clinica, II Facoltà di Medicina e Chirurgia, Ospedale "Sant'Andrea", 00189 Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Petrucca
authors.affiliation: Dipartimento di Scienze di Sanità Pubblica e Malattie Infettive, "Sapienza" Università di Roma, 00185 Rome, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Cannavacciuolo
authors.affiliation: Dipartimento di Scienze di Sanità Pubblica e Malattie Infettive, "Sapienza" Università di Roma, 00185 Rome, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Schippa
authors.affiliation: Dipartimento di Scienze di Sanità Pubblica e Malattie Infettive, "Sapienza" Università di Roma, 00185 Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Zagaglia
authors.affiliation: Dipartimento di Biologia e Biotecnologie Charles Darwin, "Sapienza" Università di Roma, 00185 Rome, Italy.
authors.forename: Milena
authors.initials: M
authors.lastname: Grossi
authors.affiliation: Dipartimento di Scienze Sperimentali e Cliniche, Università "G. D'Annunzio", 66100 Chieti, Italy. Electronic address: mauro.nicoletti@uniroma1.it.
authors.forename: Mauro
authors.initials: M
authors.lastname: Nicoletti
mesh_terms: D000942:Antigens, Bacterial / Q000378:metabolism*; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D018938:Caco-2 Cells; D016207:Cytokines / Q000378:metabolism*; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D007155:Immunologic Factors / Q000378:metabolism*; D012763:Shigella flexneri / Q000276:immunology* / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D016207:Cytokines; D007155:Immunologic Factors
keywords: IL-8; MAP kinases; PMN migration; Shigella flexneri; ospB