PT  - JOURNAL ARTICLE
AU  - Meike Voss
AU  - Bodo Wonnenber
AU  - Christian Herr
AU  - Robert Bals
AU  - Christoph Beisswenger
TI  - Epithelial NF-κB regulates bacterial translocation in the respiratory tract
DP  - 2013 Sep 01
TA  - European Respiratory Journal
PG  - P1575
VI  - 42
IP  - Suppl 57
4099  - http://erj.ersjournals.com/content/42/Suppl_57/P1575.short
4100  - http://erj.ersjournals.com/content/42/Suppl_57/P1575.full
SO  - Eur Respir J2013 Sep 01; 42
AB  - Background: Streptococcus pneumoniae (Sp) is a pathogen that colonizes the mucosal surfaces of the respiratory tract and causes severe pneumonia and invasive disease. The transcription factor NF-κB is central in the regulation of the innate immune system. It was the aim of this study to examine the function of epithelial NF-κB in regulating the translocation of Sp colonizing the upper respiratory tract into the lung and the blood stream.Methods: To generate a constitutive knockout RelA/p65 in epithelial cells relaF/F mice were crossed with CCSPCre animals to generate a relaF/F CCSP mouse line (RelA/p65). To generate mice with constitutive activated NF-κB in epithelial cells IκBαF/F mice were crossed with CCSPCre animals to generate a IκBαF/F CCSP mouse line (IκBα).The upper-respiratory tract of mice was colonized with a type 6A isolate of Sp. Survival, bacterial translocation into the lung, colonization densities and levels of cytokines were determined.Results: There was no difference in the colonization levels of Sp in the upper-respiratory tract between WT-, RelA/p65-, and IκBα-mice. IκBα-mice showed reduced bacterial translocation into the lung as compared to WT- and RelA/p65-mice. Epithelial depletion of RelA/p65 resulted in decreased survival whereas constitutively activated NF-κB resulted in enhanced survival of mice colonized with Sp. Epithelial RelA/p65 mice had increased levels of inflammatory cytokines in the lung whereas constitutive activation of NF-κB resulted in reduced cytokine levels upon bacterial colonization.Conclusion: These results show that epithelial NF-κB controls bacterial translocation from the upper-respiratory tract into the lung and invasive bacterial disease.