Modulation of Acute Diarrheal Illness by Persistent Bacterial Infection

McBee, Megan E.; Zheng, Patricia; Rogers, Arlin B.; Fox, James G.; Schauer, David B.

doi:10.1128/iai.00745-08

Cited by 20 publications

(28 citation statements)

References 47 publications

(39 reference statements)

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“…(C. rodentium infection typically results in colonic hyperplasia only after approximately 14 days of infection [refs. 63,72] and was not observed here). In contrast, gross evaluation of intestines from mice infected with C. rodentium (λstx 2dact ) showed severe destruction of the intestinal mucosa, colitis, and acute ischemic injury, with neutrophil infiltration into the muscularis layer and lamina propria and intestinal abscesses ( Figure 3B).…”

Section: Rodentium (λStx 2dact ) Causes Lethal Infection In Micementioning

confidence: 67%

A novel murine infection model for Shiga toxin–producing Escherichia coli

Mallick

McBee²,

Vanguri³

et al. 2012

J. Clin. Invest.

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106

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Enterohemorrhagic E. coli (EHEC) is an important subset of Shiga toxin-producing (Stx-producing) E. coli (STEC), pathogens that have been implicated in outbreaks of food-borne illness and can cause intestinal and systemic disease, including severe renal damage. Upon attachment to intestinal epithelium, EHEC generates "attaching and effacing" (AE) lesions characterized by intimate attachment and actin rearrangement upon host cell binding. Stx produced in the gut transverses the intestinal epithelium, causing vascular damage that leads to systemic disease. Models of EHEC infection in conventional mice do not manifest key features of disease, such as AE lesions, intestinal damage, and systemic illness. In order to develop an infection model that better reflects the pathogenesis of this subset of STEC, we constructed an Stx-producing strain of Citrobacter rodentium, a murine AE pathogen that otherwise lacks Stx. Mice infected with Stx-producing C. rodentium developed AE lesions on the intestinal epithelium and Stx-dependent intestinal inflammatory damage. Further, the mice experienced lethal infection characterized by histopathological and functional kidney damage. The development of a murine model that encompasses AE lesion formation and Stx-mediated tissue damage will provide a new platform upon which to identify EHEC alterations of host epithelium that contribute to systemic disease.

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Section: Rodentium (λStx 2dact ) Causes Lethal Infection In Micementioning

confidence: 67%

A novel murine infection model for Shiga toxin–producing Escherichia coli

Mallick

McBee²,

Vanguri³

et al. 2012

J. Clin. Invest.

Self Cite

106

View full text Add to dashboard Cite

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“…Previous reports indicate that, unlike many other pathogens, C. rodentium induces peak production of IL-1␤ 2 weeks p.i. (24), when most IL-1R Ϫ/Ϫ mice have succumbed. These data, together with our results, suggest that IL-1R signaling may instead be mediated by IL-1␣.…”

Section: Discussionmentioning

confidence: 99%

“…(13), mRNA levels do increase by 2 weeks p.i. (24), raising the possibility that IL-1R signaling, perhaps activated by IL-1␣ or the late expression of IL-1␤, provides protection.…”

mentioning

confidence: 99%

Interleukin-1 Receptor Signaling Protects Mice from Lethal Intestinal Damage Caused by the Attaching and Effacing Pathogen Citrobacter rodentium

et al. 2009

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Enteropathogenic Escherichia coli, enterohemorrhagic E. coli, and Citrobacter rodentium are classified as attaching and effacing pathogens based on their ability to adhere to the intestinal epithelium via actin-filled membranous protrusions (pedestals). Infection of mice with C. rodentium causes a breach of the intestinal epithelial barrier, leading to colitis via a vigorous inflammatory response resulting in diarrhea and a protective antibody response that clears the pathogen. Here we show that interleukin-1 receptor (IL-1R) signaling protects mice following infection with C. rodentium. Upon infection, mice lacking the type I IL-1R exhibit increased mortality together with severe colitis characterized by intramural colonic bleeding and intestinal damage including gangrenous mucosal necrosis, phenotypes also evident in MyD88-deficient mice. However, unlike MyD88 ؊/؊ mice, IL-1R ؊/؊ mice do not exhibit increased pathogen loads in the colon, delays in the recruitment of innate immune cells such as neutrophils, or defects in the capacity to replace damaged enterocytes. Further, we demonstrate that IL-1R ؊/؊ mice have an increased predisposition to intestinal damage caused by C. rodentium but not to that caused by chemical irritants, such as dextran sodium sulfate. Together, these data suggest that IL-1R signaling regulates the susceptibility of the intestinal epithelia to damage caused by C. rodentium.

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“…In contrast, in BALB/c mice which have a Th2-biased response to gastric helicobacter infection resulting in no discernible gastritis, coinfection with Toxoplasma gondii promoted a robust Th1 immune response, resulting in a progressive helicobacter-associated gastritis, gastric atrophy, and metaplasia (50). Recently, we have demonstrated that the colitis induced by Citrobacter rodentium resulted in a prolonged recovery of the disease in C57BL/6 mice when the animals were coinfected with H. hepaticus (34). It is also known that host immune responses resulting from infections with atypical mycobacteria can influ-ence how mice or humans respond immunologically to BCG vaccination (9,62).…”

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confidence: 99%

Concurrent Helicobacter bilis Infection in C57BL/6 Mice Attenuates Proinflammatory H. pylori -Induced Gastric Pathology

Lemke

Whary

et al. 2009

Infect Immun

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Because coinfections can alter helicobacter gastritis, we investigated whether enterohepatic Helicobacter bilis modulates Helicobacter pylori gastritis in C57BL/6 mice. Thirty mice per group were sham dosed, H. bilis or H. pylori infected, or H. bilis infected followed in 2 weeks by H. pylori and then evaluated at 6 and 11 months postinfection (mpi) for gastritis and premalignant lesions. Compared to H. pylori-infected mice, H. bilis/H. pylori-infected mice at 6 and 11 mpi had less severe gastritis, atrophy, mucous metaplasia and hyperplasia (P < 0.01) and, additionally, at 11 mpi, less severe intestinal metaplasia and dysplasia (P < 0.05). H. bilis/H. pylori-infected mice at 11 mpi exhibited less Ki67 labeling of proliferating epithelial cells, reduced numbers of FoxP3 ؉ T-regulatory (T REG ) cells, and lower FoxP3 ؉ mRNA levels than did H. pylori-infected mice (P < 0.05). Proinflammatory interleukin-1␤ (IL-1␤), gamma interferon, and tumor necrosis factor alpha mRNA levels were attenuated in H. bilis/H. pylori-infected mice at 6 and 11 mpi (P < 0.01), although anti-inflammatory IL-10, IL-13, and transforming growth factor ␤1 mRNA levels were not consistently impacted by H. bilis coinfection. Decreased pathology in H. bilis/H. pylori-infected mice correlated with higher gastric H. pylori colonization at 6 mpi (P < 0.001) and lower Th1-associated immunoglobulin G2c responses to H. pylori at 6 and 10 mpi (P < 0.05). We hypothesized that reduced pathology in H. bilis/H. pylori-infected mice was due to H. bilis-primed T REG cells in the lower bowel that migrated to the gastric compartment and inhibited Th1 responses to subsequent H. pylori infection. Thus, H. pylori-induced gastric lesions may vary in mouse models of unknown enteric helicobacter infection status and, importantly, variable sequelae to human H. pylori infection, particularly in developing countries, may occur where coinfection with lower bowel helicobacters and H. pylori may be common.Helicobacter pylori, first isolated by Warren and Marshall, induces a persistent infection and gastritis and is known to colonize the stomach of over 50% of the human population (2). In a subset of infected individuals, H. pylori is linked to the development of peptic ulcer disease, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. It has been classified by the World Health Organization as a class I carcinogen (25). It is not clear why some individuals infected with H. pylori develop serious disease, while others do not. Host and environmental factors, as well as the virulence properties of H. pylori, appear to play an important role in determining disease outcome (17, 52, 60). Poor socioeconomic conditions promote early acquisition and infection with H. pylori and infection rates often approach Ͼ90% in these populations. Interestingly, some African countries with especially high prevalence rates of infection have lower-than-expected rates of gastric cancer. This paradox has been referred to as "the African Enigma" (24). The low incidence of...

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Modulation of Acute Diarrheal Illness by Persistent Bacterial Infection

Cited by 20 publications

References 47 publications

A novel murine infection model for Shiga toxin–producing Escherichia coli

A novel murine infection model for Shiga toxin–producing Escherichia coli

Interleukin-1 Receptor Signaling Protects Mice from Lethal Intestinal Damage Caused by the Attaching and Effacing Pathogen Citrobacter rodentium

Concurrent Helicobacter bilis Infection in C57BL/6 Mice Attenuates Proinflammatory H. pylori -Induced Gastric Pathology

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