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

Abstract

AbstractBackgroundThe 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 againstE.colipneumonia through TLR4 signaling.MethodsC3H/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 4thweek,E.coliwas injected to trachea to induceE.colipneumonia.ResultsWe found that commensal depletion by antibiotic pretreatment beforeE.colipneumonia 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 decreasedE.colipneumonia-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.ConclusionsTaken together with that commensal depletion increasedE.colipneumonia-induced mortality and LPS supplementation decreased it, we conclude that gut flora enhances bacterial clearance againstE.colipneumonia through TLR4.