Commensal Microflora Contribute to Host Defense Against Escherichia Coli Pneumonia Through Toll-Like Receptors
- 1 July 2011
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Shock
- Vol. 36 (1), 67-75
- https://doi.org/10.1097/shk.0b013e3182184ee7
Abstract
The influence of the gut-lung axis on the lung immunity, although appreciated, remains undefined mechanically. This study was designed to investigate whether commensal microflora in gut increase host defense against subsequent pneumonia through toll-like receptor (TLR) signaling and if oral TLR4 ligand supplementation enhances lung defense against bacterial challenge. We found that commensal gut depletion by antibiotic pretreatment before Escherichia coli pneumonia challenge induced a 15-fold and a 3-fold increase in bacterial counts in blood and lung, respectively, and a 30% increase of mortality when compared with the E. coli group. Commensal depletion also induced a suppression of cytokines expression as well as nuclear factor κB activity in intestine. Furthermore, LPS supplementation during antibiotic pretreatment reversed these effects. Commensal depletion also decreased bacterial killing activity of alveolar macrophages and increased IL-6 as well as IL-1β levels and keratinocyte-derived chemokine, macrophage inflammatory protein 2, and IL-1β expression of lung, and LPS supplementation reversed them. In conclusion, commensal gut microflora in the intestinal tract appear to be critical in inducing TLR4 expression as well as nuclear factor κB activation of intestine and lung innate defense against E. coli pneumonia.Keywords
This publication has 33 references indexed in Scilit:
- Role of Gut Commensal Microflora in the Development of Experimental Autoimmune EncephalomyelitisPublished by The American Association of Immunologists ,2009
- Acute phase response impairs host defense against Pseudomonas aeruginosa pneumonia in mice*Critical Care Medicine, 2008
- Hypertonic saline enhances host defense to bacterial challenge by augmenting Toll-like receptors*Critical Care Medicine, 2006
- Signal transduction by the lipopolysaccharide receptor, Toll‐like receptor‐4Immunology, 2004
- Getting a grip on things: how do communities of bacterial symbionts become established in our intestine?Nature Immunology, 2004
- Imbalanced secretion of IL-1 and IL-1RA in Chlamydia pneumoniae-infected mononuclear cells from COPD patientsEuropean Respiratory Journal, 2003
- Gene expression in human neutrophils during activation and priming by bacterial lipopolysaccharideJournal of Cellular Biochemistry, 2003
- Toll-like receptors and innate immunityNature Reviews Immunology, 2001
- Role of NF-κB in immune and inflammatory responses in the gutGut, 1998
- Enteral nutrition in the critically ill patient: A critical review of the evidenceIntensive Care Medicine, 1993