ASalmonella entericaSerovar Typhimurium Translocated Leucine-Rich Repeat Effector Protein Inhibits NF-κB-Dependent Gene Expression

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Abstract
Nontyphoidal salmonellae are enteric pathogens that cause acute gastroenteritis and colonize the intestinal tract for prolonged periods. In the intestinal epithelia, these bacteria induce secretion of proinflammatory cytokines, such as interleukin-8 (IL-8), which leads to a profound inflammatory response through recruitment of polymorphonuclear leukocytes. Production of IL-8 induced bySalmonellaspp. is due to the activation of the transcription factors nuclear factor κB (NF-κB) and activator protein-1 (AP-1). This work demonstrates thatSalmonella entericaserovar Typhimurium can downmodulate IL-8 production after invasion of intestinal epithelial cells. TheSalmonellatranslocated effector proteins SspH1 and SptP participate in this process. SspH1 is a member of the bacterial LPX repeat protein family that localizes to the mammalian nucleus and inhibits NF-κB-dependent gene expression. AShigella flexneritranslocated effector, IpaH9.8, which has a similar structure and subcellular localization in mammalian cells, also inhibits NF-κB-dependent gene expression. We propose that suppression of inflammatory responses by intracellularS. entericaserovar Typhimurium, and perhapsShigella flexneri, contributes to bacterial colonization of host tissues and pathogenesis.