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

Victoni, T. et al. (2010) Local and remote tissue injury upon intestinal ischemia and reperfusion depends on the TLR/MyD88 signaling pathway. Medical Microbiology and Immunology, 199(1), pp. 35-42. (doi: 10.1007/s00430-009-0134-5)

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-alpha and IL-1 beta level. Furthermore, diminished microvascular leak and bacteremia were associated with enhanced survival of MyD88(-/-) mice. However, neither TNF-alpha nor IL-1 beta 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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Guabiraba Brito, Dr Rodrigo
• Authors: Victoni, T., Coelho, F.R., Soares, A.L., Freitas, A., Secher, T., Guabiraba Brito, R., Erard, F., Oliveira-Filho, R.M., Vargaftig, B.B., Lauvaux, G., Kamal, M.A., Ryffel, B., Moser, R., and Tavares-de-Lima, W.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Medical Microbiology and Immunology
• ISSN: 0300-8584