NF-κB activation is critical for bacterial lipoprotein tolerance-enhanced bactericidal activity in macrophages during microbial infection

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dc.contributor.authorLiu, Jinghua
dc.contributor.authorXiang, Jing
dc.contributor.authorLi, Xue
dc.contributor.authorBlankson, Siobhan
dc.contributor.authorZhao, Shuqi
dc.contributor.authorCai, Junwei
dc.contributor.authorJiang, Yong
dc.contributor.authorRedmond, H. Paul
dc.contributor.authorWang, Jiang Huai
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderNational Natural Science Foundation of Chinaen
dc.contributor.funderNatural Science Foundation of Guangdong Provinceen
dc.date.accessioned2017-01-26T15:50:09Z
dc.date.available2017-01-26T15:50:09Z
dc.date.issued2017-01-12
dc.date.updated2017-01-26T15:41:55Z
dc.description.abstractTolerance to bacterial components represents an essential regulatory mechanism during bacterial infection. Bacterial lipoprotein (BLP)-induced tolerance confers protection against microbial sepsis by attenuating inflammatory responses and augmenting antimicrobial activity in innate phagocytes. It has been well-documented that BLP tolerance-attenuated proinflammatory cytokine production is associated with suppressed TLR2 signalling pathway; however, the underlying mechanism(s) involved in BLP tolerance-enhanced antimicrobial activity is unclear. Here we report that BLP-tolerised macrophages exhibited accelerated phagosome maturation and enhanced bactericidal activity upon bacterial infection, with upregulated expression of membrane-trafficking regulators and lysosomal enzymes. Notably, bacterial challenge resulted in a strong activation of NF-κB pathway in BLP-tolerised macrophages. Importantly, activation of NF-κB pathway is critical for BLP tolerance-enhanced antimicrobial activity, as deactivation of NF-κB in BLP-tolerised macrophages impaired phagosome maturation and intracellular killing of the ingested bacteria. Finally, activation of NF-κB pathway in BLP-tolerised macrophages was dependent on NOD1 and NOD2 signalling, as knocking-down NOD1 and NOD2 substantially inhibited bacteria-induced activation of NF-κB and overexpression of Rab10 and Acp5, two membrane-trafficking regulators and lysosomal enzymes contributed to BLP tolerance-enhanced bactericidal activity. These results indicate that activation of NF-κB pathway is essential for BLP tolerance-augmented antimicrobial activity in innate phagocytes and depends primarily on both NOD1 and NOD2.en
dc.description.sponsorshipScience Foundation Ireland (SFI Research Frontiers Programme (GrantSFI/08/RFP/BIC1734); National Natural Science Foundation of China (Grants 81072425, 81272149, 81471901); Natural Science Foundation of Guangdong Province (Grant 2015A030311031)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationLiu, J., Xiang, J., Li, X., Blankson, S., Zhao, S., Cai, J., Jiang, Y., Redmond, H. P. and Wang, J. H. (2017) 'NF-κB activation is critical for bacterial lipoprotein tolerance-enhanced bactericidal activity in macrophages during microbial infection', Scientific Reports, 7, pp. 40418. doi:10.1038/srep40418en
dc.identifier.doi10.1038/srep40418
dc.identifier.endpage40418-15en
dc.identifier.issn2045-2322
dc.identifier.journaltitleScientific Reportsen
dc.identifier.startpage40418-1en
dc.identifier.urihttps://hdl.handle.net/10468/3527
dc.identifier.volume7en
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.rights© The Author(s) 2017. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectInfectionen
dc.subjectInnate immunityen
dc.subjectBacterial infectionen
dc.subjectToleranceen
dc.titleNF-κB activation is critical for bacterial lipoprotein tolerance-enhanced bactericidal activity in macrophages during microbial infectionen
dc.typeArticle (peer-reviewed)en
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