Gut flora enhance bacterial clearance in lung through toll-like receptors 4

• Main Authors: Hsu Ching-Mei, Chen Pei-Hsuan, Yang Ming-Chieh, Tsay Tzyy-Bin, Chen Lee-Wei
• Format: Article
• Language: English
• Published: BMC 2011-09-01
• Series: Journal of Biomedical Science
• Subjects: gut flora; pneumonia; lipopolysaccharide; Toll-like receptors; NF-κB
• Online Access: http://www.jbiomedsci.com/content/18/1/68
• ISSN: 1021-7770; 1423-0127

<p>Abstract</p> <p>Background</p> <p>The influence of the gut flora on lung inflammatory reaction against bacterial challenge remains undefined. This study was designed to investigate whether gut flora enhances lung defense against <it>E.coli </it>pneumonia through TLR4 signaling.</p> <p>Methods</p> <p>C3H/HeN (WT) mice and C3H/HeJ (TLR4 deficient) mice were treated with antibiotics in drinking water for 4 weeks to deplete gut commensal microflora. At week 3, drinking water was supplemented with lipopolysaccharide (LPS); a ligand for TLR4, to trigger TLRs in intestinal tract. At the end of 4^thweek, <it>E.coli </it>was injected to trachea to induce <it>E.coli </it>pneumonia.</p> <p>Results</p> <p>We found that commensal depletion by antibiotic pretreatment before <it>E.coli </it>pneumonia challenge induced a 30% decrease of MPO activity in the lung, a significant decrease of bacterial killing activity of alveolar macrophage, and bacterial counts in C3H/HeN mice but not in C3H/HeJ (TLR4 deficient) mice. LPS, a TLR4 ligand, supplementation during antibiotic pretreatment reversed these effects and decreased <it>E.coli </it>pneumonia-induced mortality in C3H/HeN mice. Furthermore, commensal depletion induced a suppression of NF-κB DNA binding activity and an increase of KC, MIP-2, IL-1β expression in the lung in C3H/HeN mice but not in C3H/HeJ mice.</p> <p>Conclusions</p> <p>Taken together with that commensal depletion increased <it>E.coli </it>pneumonia-induced mortality and LPS supplementation decreased it, we conclude that gut flora enhances bacterial clearance against <it>E.coli </it>pneumonia through TLR4.</p>