Chapter 24 : spp.: Masters of Inflammation

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This chapter highlights recent progress made toward understanding the molecular basis of -induced enteritis. Information is scarce on the specific course of events following nontyphoidal infection in humans because most infected individuals are rarely hospitalized. As such, observations of nontyphoidal infection have mostly come from patients admitted to the hospital with severe fatal infections. Interactions between bacteria and intestinal tissue were examined in starved, opium-treated guinea pigs several hours after oral challenge with 10 invasive serovar Typhimurium. This study found that closely contacts the epithelial cells lining the intestine, primarily the ileum, and thereafter elicits the local degeneration of filamentous actin in apical microvilli and the underlying terminal web. More recently, studies have turned to the use of cattle to model the pathophysiology of -induced enteritis in humans. Following nitrogen mustard administration, the rabbit ligated ileal loops were then infected with serovar Typhimurium for 72 h. Results from this study revealed that nitrogen mustard treatment markedly inhibited serovar Typhimurium-induced secretion. This inflammatory response greatly contributes to the pathophysiology of the infection, exhibited by typical inflammatory diarrhea. Recent work has begun to disclose the molecular and cellular events involved in this complex phenomenon. In addition to TTSS-1-associated genes, several other genes affecting enteropathogenicity are currently being investigated.

Citation: McCormick B. 2003. spp.: Masters of Inflammation, p 439-454. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch24
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Image of FIGURE 1

Cl secretory pathways induced by during infection. The intracellular SopB protein affects inositol phosphate (IP) signaling events. One such event is the transient increase in IP4, which antagonizes the closure of chloride channels influencing net electrolyte transport and, hence, fluid secretion. Infection of epithelial cells also results in the production of PGs such as PGE, which can further lead to Cl secretion. Finally, Cl release can be initiated by apically located and activated PMN. These PMN release 5′-AMP, which, through a series of steps, triggers signaling cascades involving cyclic AMP and thus promotes the opening of apical Cl channels.

Citation: McCormick B. 2003. spp.: Masters of Inflammation, p 439-454. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch24
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Image of FIGURE 2

Model of proposed events affecting -induced PMN transmigration across the intestinal epithelium. spp. evoke a potent inflammatory response in the host, the hallmark of which is the migration of PMN across the intestinal mucosa. This process includes extravasation of circulating PMN from the microvasculature, passage of PMN across the lamina propria, and paracellular movement of PMN across the epithelium. PMN recruitment is coordinated by the release of proinflammatory cytokines, among which are IL-8 and PEEC. interaction with enterocytes delivers Sop proteins into the cell cytoplasm via a TTS-dependent pathway. These Sop proteins play a role in enteropathogenic responses in the intestinal mucosa. Intracellular bacteria reside within membrane-bound vesicles and possibly continue to translocate TTSS-1-secreted effectors. By an unknown mechanism, invasion also causes the transcellular transport of flagellin to the basolateral membrane domain, where it promotes the release of IL-8 by interacting with TLR-5. Concurrently, the TTSS-1 product, SipA, was found to be both necessary and sufficient for induction of PMN transmigration across model intestinal epithelia in a PKC-dependent manner.

Citation: McCormick B. 2003. spp.: Masters of Inflammation, p 439-454. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch24
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Image of FIGURE 3

Model of serovar Typhimurium-induced signaling in epithelial cells by the -secreted protein SipA. Interaction of the serovar Typhimuriumsecreted effector protein SipA with the apical domain of polarized epithelial cells leads to activation of ARF6 (GTP-ARF6) at the apical membrane, most likely through the mammalian guanine exchange factor (GEF) ARNO. This leads to an increase in PLD activity and local production of PA, which is metabolized to DAG by PA phosphohydrolase (PAP). Generation of DAG recruits PKC to the apical membrane. Activation of PKC at this site (PKC) is necessary for the apical release of the chemokine PEEC and subsequent basolateral-to-apical PMN transmigration.

Citation: McCormick B. 2003. spp.: Masters of Inflammation, p 439-454. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch24
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