Proinflammatory signal transduction pathway induced by Shigella flexneri porins in caco-2 cells

Abstract

The recognition of bacterial components on the intestinal epithelial cells occurs through the toll-like receptors and is followed by the induction of an effective innate immune response. We analyzed receptor expression and signaling pathways involved in activation of human colon adenocarcinoma cells after stimulation with porins and LPS of Shigella flexneri. We also analyzed the expression and production of some cytokines, of intercellular adhesion molecule-1, of antimicrobial peptides human β-defensins, and of the inducible form of nitric oxide synthase. Our data demonstrate that TLR2 is involved in porin recognition, whereas TLR4 with MD2, is required for LPS recognition.

Differential Host Immune Responses to Epidemic and Endemic Strains of <i>Shigella dysenteriae <i> Type 1

“…This variation may give the epidemic strain an edge above the endemic strains in evoking pro-inflammatory responses and severity of the disease during epidemics. For example, the ability of bacterial protiens, such as S. flexneri porins to activate Toll-like receptors (TLR-2), thereby stimulating the production and release of proinflammatory cytokines, adhesion molecules, and nitric oxide, suggests a possible role of these bacterial proteins in inflammation ( 25 ). Many proteins of the epidemic S. dysenteriae type 1, such as type III secretion system, energyy metabolism, acid resistance may also play a significant role in the increased virulence of the epidemic S. dysenteriae type 1 strain ( 26 ).…”

Inflammatory Response to Different Toxins in Experimental Sepsis Models

“…They may act as a PAMP both alone and cooperatively with LPS. TLR2 recognizes Shigella flexneri porins and triggers upstream NF-κB activation as with LPS administration via convergent pathways, but differential cytokine production occurs [68]. Neisserial porins also signal in a TLR2 dependent fashion [69].…”

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 ).…”