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

Journal of Biomedical Science

Lee-Wei Chen⁴  Ching-Mei Hsu²  Pei-Hsuan Chen¹  Ming-Chieh Yang¹  Tzyy-Bin Tsay³ 

[1] Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan;Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan;Department of Surgery, Zuoying Armed Forces General Hospital, Kaohsiung, Taiwan;Institute of Emergency and Critical Care Medicine, National Yang-Ming University, Taipei, Taiwan

关键词: NF-κB;    Toll-like receptors;    lipopolysaccharide;    pneumonia;    gut flora;   

Others  :  829402
DOI  :  10.1186/1423-0127-18-68

 received in 2011-04-24, accepted in 2011-09-10,  发布年份 2011

【 摘 要 】

Background

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 E.coli pneumonia through TLR4 signaling.

Methods

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^th week, E.coli was injected to trachea to induce E.coli pneumonia.

Results

We found that commensal depletion by antibiotic pretreatment before E.coli 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 E.coli 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.

Conclusions

Taken together with that commensal depletion increased E.coli pneumonia-induced mortality and LPS supplementation decreased it, we conclude that gut flora enhances bacterial clearance against E.coli pneumonia through TLR4.

【 授权许可】

   
2011 Tsay et al; licensee BioMed Central Ltd.

【 图 表 】

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