A Role for Tumor Necrosis Factor- α in the Increased Mortality Associated with Vibrio Vulnificus Infection in the Presence of Hepatic Dysfunction

Espat, N. Joseph; Auffenberg, Troy; Abouhamze, Amer; Baumhofer, Julie; Moldawer, Lyle L.; Howard, Richard J.

doi:10.1097/00000658-199604000-00012

Cited by 38 publications

(32 citation statements)

References 14 publications

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“…Additionally, CPS production is believed to constitute a primary virulence factor of V. vulnificus, which is essential for pathogenicity (5,22). The production of proinflammatory cytokines such as IL-1ß, TNF-·, and IL-6 has been reported in V. vulnificus-infected hosts (12)(13)(14)40). Our data demonstrated that TLR2 is the key receptor for V. vulnificus CPS-related immune response.…”

Section: Discussionsupporting

confidence: 53%

“…The majority of fatal cases are attributable to septic shock which results from a variety of virulence factors of V. vulnificus including lipopolysaccharide (LPS) (3), capsular polysaccharide (CPS) (4-6), siderophores (7), cytolysin (8), elastolytic protease (9), phospholipase A 2 (10), RTX toxin (rtxA) (11) and flagella (12). These virulence factors may persistently activate the generation of proinflammatory mediators such as tumor necrosis factor-· from the affected host (4,13,14). In particular, surface polysaccharides, including CPS and LPS, perform pivotal roles in the pathogenicity of gram-negative bacteria by assisting the bacteria in the evasion of host defenses (4,15).…”

Section: Introductionmentioning

confidence: 99%

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Involvement of capsular polysaccharide via a TLR2/NF-κB pathway in Vibrio vulnificus-induced IL-8 secretion of human intestinal epithelial cells

Lee

Kim²,

Choi

et al. 2010

Int J Mol Med

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Abstract. In a previous study, we reported that a wbpP gene mutation in Vibrio vulnificus was significantly impaired in its ability to synthesize surface capsular polysaccharide (CPS). In this study, we evaluated the functions of the V. vulnificus capsular polysaccharide on interleukin (IL)-8 production, as well as its underlying mechanisms in human intestinal epithelial cells. The CPS-defective wbpP mutant induced significantly lower levels of IL-8 production, IL-8 gene promoter activation and NF-κB activity in INT-407 cells than was noted with the wild-type or wbpP-complemented V. vulnificus. The expression levels of Toll-like receptor (TLR)2 mRNA and protein were also found to be lower in INT-407 cells infected with the CPS-defective wbpP mutant than in those cells infected with the wild-type or the wbpPcomplemented strains. Additionally, the treatment of INT-407 cells with anti-TLR2 antibody proved to significantly block IL-8 production and NF-κB minimal promoter activity induced by the wild-type or the wbpP-complemented strains. Furthermore, purified V. vulnificus CPS was found to significantly induce IL-8 production and NF-κB activation, both of which were inhibited upon the addition of the anti-TLR2 antibody. Taken together, these results demonstrate that V. vulnificus capsular polysaccharide is involved in the induction of IL-8 production of human intestinal epithelial cells via a TLR2/NF-κB-dependent pathway.

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Section: Discussionsupporting

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Involvement of capsular polysaccharide via a TLR2/NF-κB pathway in Vibrio vulnificus-induced IL-8 secretion of human intestinal epithelial cells

Lee

Kim²,

Choi

et al. 2010

Int J Mol Med

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“…Therefore, while much is now known about some of the bacterial factors involved in the disease process, little is understood about host cellular factors leading to susceptibility. It has been previously shown that V. vulnificus has the ability to elicit inflammationassociated cytokines from primary human cells in vitro and from animals in vivo (10,33). A recent study from Korea is the first to report significant increases in the levels of pro-inflammatory cytokines tumor necrosis factor alpha (TNF-␣), interleukin-1␤ (IL-1␤), and IL-6 in serum from V. vulnificus-infected patients compared to healthy individuals, confirming a role for dysregulation of the cytokine response (39).…”

mentioning

confidence: 99%

Inflammatory Cytokine Response to Vibrio vulnificus Elicited by Peripheral Blood Mononuclear Cells from Chronic Alcohol Users Is Associated with Biomarkers of Cellular Oxidative Stress

et al. 2003

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Vibrio vulnificus is the leading cause of death in the United States associated with the consumption of raw seafood, particularly oysters. In epidemiological studies, primary septicemia and inflammation-mediated septic shock caused by V. vulnificus is strongly associated with liver disease, often in the context of chronic alcohol abuse. The present study was undertaken to determine whether clinical biomarkers of liver function or cellular oxidative stress are associated with peripheral blood mononuclear cell inflammatory cytokine responses to V. vulnificus. Levels of interleukin-1␤ (IL-1␤), IL-6, IL-8, and tumor necrosis factor alpha elicited in response to V. vulnificus and measured in cell supernatants were not associated with the liver biomarkers aspartate aminotransferase (AST) or alanine aminotransferase (ALT) or the AST/ALT ratio. Vibrio vulnificus is a gram-negative bacterium found commonly in marine and estuarine environments. In the United States, it predominates in the warm waters of the Gulf and Atlantic Coasts (25, 27, 28). Despite not being a notifiable disease, each year there are 20 to 50 reported cases of V. vulnificus primary septicemia in the United States, occurring most often following the consumption of naturally contaminated raw oysters (2, 14). V. vulnificus also has the ability to cause gastroenteritis, which is generally self-limiting, and wound infections in otherwise healthy individuals (17, 32). Primary septicemia is seen almost exclusively in people with an underlying condition affecting their immune system. In epidemiological studies, primary septicemia caused by V. vulnificus is most often associated with preexisting liver disease, although other conditions, such as diabetes mellitus, hemochromatosis, immunodeficiency, or malignancy, may also increase susceptibility to this organism (2,14,17,24,41). The impairment of iron metabolism and resultant iron overload associated with many of these conditions is thought to support increased V. vulnificus growth and reduced immune clearance (1, 15, 16). Primary septicemia caused by V. vulnificus appears to follow a classical septic shock pathway, including an overwhelming inflammatory cytokine response followed by multiorgan failure and death. Presently, there is no effective treatment for V. vulnificus once someone has developed primary septicemia, and death usually ensues. It should be noted that V. vulnificus has many similarities with other gram-negative, encapsulated, opportunistic bacterial pathogens and likely exploits similar host susceptibility pathways that could be targeted for intervention.To date, the majority of V. vulnificus studies have focused on the bacterial factors involved in disease (41). Therefore, while much is now known about some of the bacterial factors involved in the disease process, little is understood about host cellular factors leading to susceptibility. It has been previously shown that V. vulnificus has the ability to elicit inflammationassociated cytokines from primary human cells in vitro and from animals...

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“…These host-or bacteria-derived factors may persistently activate the generation of proinflammatory mediators such as tumor necrosis factor-α, IL-1β, IL-6, IL-8, and nitric oxide from affected hosts (10,11). The majority of these mediators display multiple biological effects, and have been identified as key mediators in the pathophysiological alterations associated with septic shock.…”

Section: Introductionmentioning

confidence: 99%

Comparative analysis of proteins in the culture supernatants of human intestinal epithelial cells infected with the wild-type and rtxE mutant of Vibrio vulnificus

Lee

Kim²,

Choi

et al. 2011

Int J Mol Med

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Abstract. Bacterial virulence factors and secreted extracellular proteins from damaged host cells following infection have been recognized as key mediators in the pathophysiological alterations observed in septic shock, and have also been shown to have a synergistic influence on bacterial pathogenicity. We hypothesized that during infections, virulence factors as well as host-shed proteins may synergistically influence aspects of the pathogenicity of V. vulnificus, such as primary septic shock and overproduction of proinflammatory cytokines. However, virulence factors and host-derived proteins have yet to be clearly evaluated during V. vulnificus infection. In this study, we analyzed and compared the proteins in conditioned supernatants generated from co-cultures of host cells and either wild-type or rtxE mutant V. vulnificus using LC-QTOF-MS/ MS analysis. In a previous study, we determined that the culture supernatants of the rtxE mutant V. vulnificus-infected INT-407 cells induced significantly lower levels of IL-8 production from human intestinal epithelial cells than did the culture supernatants of wild-type V. vulnificus-infected INT-407 cells. LC-QTOF-MS/MS analysis results demonstrated that levels of proteins such as HSP90 α/β, 14-3-3 γ, PRX II, hnRNP K, β-actin, α-tubulin and V. vulnificus flagellin were significantly lower in the culture supernatants of rtxE mutant V. vulnificusinfected INT-407 cells than in the culture supernatants of wild-type V. vulnificus-infected INT-407 cells. These results demonstrate that V. vulnificus RTX toxins acting via rtxE, a transporter of virulence factors, play a very important role in the pathogenesis of V. vulnificus, as well as in its initial role in inducing pathogenic mediators from host cells.

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A Role for Tumor Necrosis Factor- α in the Increased Mortality Associated with Vibrio Vulnificus Infection in the Presence of Hepatic Dysfunction

Abstract: Cirrhotic mice show increased mortality to Vibrio infection, and this increased mortality is dependent on an in vivo tumor necrosis factor-alpha response.

Cited by 38 publications

References 14 publications

Involvement of capsular polysaccharide via a TLR2/NF-κB pathway in Vibrio vulnificus-induced IL-8 secretion of human intestinal epithelial cells

Involvement of capsular polysaccharide via a TLR2/NF-κB pathway in Vibrio vulnificus-induced IL-8 secretion of human intestinal epithelial cells

Inflammatory Cytokine Response to Vibrio vulnificus Elicited by Peripheral Blood Mononuclear Cells from Chronic Alcohol Users Is Associated with Biomarkers of Cellular Oxidative Stress

Comparative analysis of proteins in the culture supernatants of human intestinal epithelial cells infected with the wild-type and rtxE mutant of Vibrio vulnificus

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