Outer Membrane Protein A (OmpA) of Shigella flexneri 2a Links Innate and Adaptive Immunity in a TLR2-dependent Manner and Involvement of IL-12 and Nitric Oxide

Abstract

Background: OmpA activates innate immunity through TLR2, but its function and mechanism of targeting adaptive immunity remains unexplored. Results: TLR2 regulates OmpA processing and presentation, NO and cytokine release, which contributes to development of type-1 adaptive immunity. Conclusion: TLR2 is crucial to link innate and adaptive responses stimulated by OmpA. Significance: S. flexneri 2a OmpA, a novel molecule, coordinates the innate and adaptive responses.

Immuno-Modulatory Role of Porins: Host Immune Responses, Signaling Mechanisms and Vaccine Potential

“…Porins from many gram-negative bacteria such as Fusobacterium nucleatum , Haemophilus infl uenza e, Helicobater pylori , Neisseria , Salmonella and Shigella spp. induce pro-infl ammatory cytokines like TNFα, IL-6 and IL-1β secretion in a variety of cell lines and primary cells, such as monocytes and macrophages of human and mouse origin (Table 6.1 ) (Tufano et al 1994(Tufano et al , 1995Toussi et al 2012 ;Galdiero et al 2001aGaldiero et al , b , 2004Vitiello et al 2004Vitiello et al , 2011Liu et al 2010 ;Singleton et al 2005 ;Massari et al 2006 ;Al-Bader et al 2004 ;Moreno-Eutimio et al 2013, Galdiero et al 2005, 2006aRay et al 2003 ;Biswas et al 2007 ;Elena et al 2009 ;Pore et al 2012 ). Vibrio cholerae OmpU stimulates monocytes and macrophages to produce TNFα and IL-6 (Sakharwade et al 2013 ).…”

“…PorA of Neisseria meningitidis induces IL-12 secretion in human PBMCs (peripheral blood mononuclear cells) derived DCs (Al-Bader et al 2004 ). Salmonella porins, OmpA of Shigella fl exineri and OmpU of V. cholerae are able to stimulate nitric oxide production in macrophages of mouse origin (Sakharwade et al 2013 ;Pore et al 2012 ;Gupta et al 1999 ). In contrast to the reports demonstrating porin-induced pro-infl ammatory responses, Salmonella porins which are pro-infl ammatory in nature can also induce the production of IL-10, a potent immune-suppressive cytokine in human cell line and mouse primary cells (Galdiero et al 2005 ).…”

Functional properties of the major outer membrane protein in Stenotrophomonas maltophilia

“…Many OmpA family proteins are known to be involved in bacterial pathogenesis and are capable of activating innate immunity and inducing cytotoxic responses (Khan et al, 2003;Mortensen and Skaar, 2012;Pore et al, 2012). To test the cytotoxic effect of MopB, we incubated wild-type and mopB mutant bacterial cells with L929 fibroblasts, and determined the number of dead fibroblast cells as described in 'Materials and Methods'.…”

Amino terminus mutant OmpA from an isolated antibiotic resistant <i>Escherichia</i> <i>coli</i> still possess resistance to environmental stresses

“…Furthermore, OmpA has been an ideal model for studies on the membrane protein structure and folding dynamics [8]. Similarly, OmpA homologs and OmpA-like proteins also have been suggested to exhibit the described roles [13][14][15].…”

“…In addition, the N-terminal domain of OmpA is closely related with the formation of ion channel [22]. Since OmpA is an abundant protein, it has been developed as an important target in defense against bacterial pathogens [14,23]. Increasing literatures regarding to antibiotic resistant E. coli have been reported [7].…”