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Local and remote tissue injury upon intestinal ischemia and reperfusion depends on the TLR/MyD88 signaling pathway

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An Erratum to this article was published on 22 December 2009

Abstract

Innate immune responses against microorganisms may be mediated by Toll-like receptors (TLRs). Intestinal ischemia–reperfusion (i-I/R) leads to the translocation of bacteria and/or bacterial products such as endotoxin, which activate TLRs leading to acute intestinal and lung injury and inflammation observed upon gut trauma. Here, we investigated the role of TLR activation by using mice deficient for the common TLR adaptor protein myeloid differentiation factor 88 (MyD88) on local and remote inflammation following intestinal ischemia. Balb/c and MyD88−/− mice were subjected to occlusion of the superior mesenteric artery (45 min) followed by intestinal reperfusion (4 h). Acute neutrophil recruitment into the intestinal wall and the lung was significantly diminished in MyD88−/− after i-I/R, which was confirmed microscopically. Diminished neutrophil recruitment was accompanied with reduced concentration of TNF-α and IL-1β level. Furthermore, diminished microvascular leak and bacteremia were associated with enhanced survival of MyD88−/− mice. However, neither TNF-α nor IL-1β neutralization prevented neutrophil recruitment into the lung but attenuated intestinal inflammation upon i-I/R. In conclusion, our data demonstrate that disruption of the TLR/MyD88 pathway in mice attenuates acute intestinal and lung injury, inflammation, and endothelial damage allowing enhanced survival.

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Acknowledgments

This work was supported by grants from Fondation pour la Recherche Medicale (F.R.M., France), the European Community, EC (TB REACT Contract n° 028190) and from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (02/06606-3, 04/14128-0) and Conselho Nacional de Pesquisa (CNPq). F.R. Coelho is FAPESP fellowships. W. Tavares-de-Lima is a fellow researcher of CNPq.

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Authors and Affiliations

  1. Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, 05508-900, Brazil

    Tatiana Victoni, Fernando Rodrigues Coelho, Alexandre Learth Soares, Ricardo Martins de Oliveira-Filho, B. Boris Vargaftig & Wothan Tavares-de-Lima

  2. Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, 14049-900, Brazil

    Andressa de Freitas

  3. Molecular Immunology and Embryology, University and CNRS, UMR6218, Cedex 2, 45071, Orléans, France

    Thomas Secher, Rodrigo Guabiraba, François Erard, Mamdouh A. Kamal & Bernhard Ryffel

  4. CIML-Centre d’Immunologie Marseille-Luminy, Cedex 09, F13288, Marseille, France

    Gregoire Lauvaux

  5. Biomedical Research Foundation, Lauchefeld 31, 9548, Matzingen, Switzerland

    René Moser

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  1. Tatiana Victoni
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Corresponding author

Correspondence to Bernhard Ryffel.

Additional information

T. Victoni and F. R. Coelho contributed equally to this work.

An erratum to this article can be found at http://dx.doi.org/10.1007/s00430-009-0140-7

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Victoni, T., Coelho, F.R., Soares, A.L. et al. Local and remote tissue injury upon intestinal ischemia and reperfusion depends on the TLR/MyD88 signaling pathway. Med Microbiol Immunol 199, 35–42 (2010). https://doi.org/10.1007/s00430-009-0134-5

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