Alteration of intestinal intraepithelial lymphocytes and increased bacterial translocation in a murine model of cirrhosis

Inamura, Toshiaki; Miura, Soichiro; Tsuzuki, Yoshikazu; Hara, Yuriko; Hokari, Ryota; Ogawa, Tetsuhei; Teramoto, Ken; Watanabe, Chikako; Kobayashi, Hisashi; Nagata, Hiroshi; Ishii, Hiromasa

doi:10.1016/j.imlet.2003.05.002

Cited by 31 publications

(18 citation statements)

References 33 publications

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“…It is well established that liver injury is associated with increased intestinal permeability, a phenomenon designated 'leaky gut', and which contributes at least in part to the observed rise in bacterial cell wall products in the portal tracts. 1 This phenomenon has been demonstrated by the presence in the portal tract of entire bacterial pathogen products such as LPS at an early stage of liver injury. 20,21 It is likely that small compounds such as MDP also cross the digestive barrier, but at an earlier stage.…”

Section: Discussionmentioning

confidence: 99%

“…The latter contributes to a rise in bacterial cell wall products, also called pathogen-associated molecular patterns (PAMP), in portal tracts. 1 PAMP may enhance inflammatory processes within the liver through their interaction with pathogen recognition receptors. It has recently been suggested that peptidoglycan, a cell wall product common to both Grampositive and Gram-negative bacteria, may be an important inducer of the proinflammatory process in the digestive tract.…”

mentioning

confidence: 99%

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NOD2: a potential target for regulating liver injury

Body-Malapel

Dharancy

Berrebi

et al. 2008

Laboratory Investigation

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The recent discovery of bacterial receptors such as NOD2 that contribute to crosstalk between innate and adaptive immune systems in the digestive tract constitutes an important challenge in our understanding of liver injury mechanisms. The present study focuses on NOD2 functions during liver injury. NOD2, TNF-a and IFN-g mRNA were quantified using real-time PCR in liver samples from patients and mice with liver injury. We evaluated the susceptibility of concanavalin A (ConA) challenge in NOD2-deficient mice (Nod2 À/À ) compared to wild-type littermates. We tested the effect of muramyl dipeptide (MDP), the specific activator of NOD2, on ConA-induced liver injury in C57BL/6 mice. We studied the cellular distribution and the role of NOD2 in immune cells and hepatocytes. We demonstrated that NOD2, TNF-a and IFN-g were upregulated during liver injury in mice and humans. Nod2 À/À mice were resistant to ConA-induced hepatitis compared to their wild-type littermates, through reduced IFN-g production by immune cells. Conversely, administration of MDP exacerbated ConA-induced liver injury. MDP was a strong inducer of IFN-g in freshly isolated human PBMC, splenocytes and hepatocytes. Our study supports the hypothesis that NOD2 contributes to liver injury via a regulatory mechanism affecting immune cells infiltrating the liver and hepatocytes. Taken together, our results indicate that NOD2 may represent a new therapeutic target in liver diseases.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

NOD2: a potential target for regulating liver injury

Body-Malapel

Dharancy

Berrebi

et al. 2008

Laboratory Investigation

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“…An increased number of intraepithelial lymphocytes with markedly impaired proliferative activity and capacity for production of interferon-c have been reported in a murine model, with these changes correlating with increased bacterial translocation [12]. Whether this mechanism is important in the clinical situation is unknown.…”

Section: Pathogenesismentioning

confidence: 99%

“…The high prevalence of associated malnutrition in cirrhotic patients [11] exacerbates the potential for infection. Impairment of mucosal immunity may also be important [12].…”

mentioning

confidence: 99%

The intestinal flora and bacterial infection in cirrhosis

Riordan

Williams

2006

Journal of Hepatology

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“…Patients with chronic hepatitis are known to be abnormally susceptible to infection as a result of multiple immunologic defects [1][2][3][4][5][6] . The incidence of bacteriemia in chronic liver disease is 5-to 7-fold higher than that found in other hospitalized patients [7] .…”

Section: Introductionmentioning

confidence: 99%