title: Commensal microflora contribute to host defense against Escherichia coli pneumonia through Toll-like receptors.
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.
authors.affiliation: Institute of Emergency and Critical Care Medicine, National Yang-Ming University, Kaohsiung, Taiwan. chenlw2001@yahoo.com.tw
authors.forename: Lee-Wei
authors.initials: LW
authors.lastname: Chen
authors.forename: Pei-Hsuan
authors.initials: PH
authors.lastname: Chen
authors.forename: Ching-Mei
authors.initials: CM
authors.lastname: Hsu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D054426:Chemokine CXCL2; D004797:Enzyme-Linked Immunosorbent Assay; D004927:Escherichia coli Infections / Q000276:immunology* / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000382:microbiology*; D007113:Immunity, Innate / Q000502:physiology; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000382:microbiology; D016676:Macrophages, Alveolar / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000382:microbiology*; D016133:Polymerase Chain Reaction; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D054426:Chemokine CXCL2; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors