Activation of both TLR and NOD signaling confers host innate immunity-mediated protection against microbial infection

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dc.contributor.authorZhou, Huiting
dc.contributor.authorCoveney, Andrew P.
dc.contributor.authorWu, Ming
dc.contributor.authorHuang, Jie
dc.contributor.authorBlankson, Siobhan
dc.contributor.authorZhao, He
dc.contributor.authorO'Leary, D. Peter
dc.contributor.authorBai, Zhenjiang
dc.contributor.authorLi, Yiping
dc.contributor.authorRedmond, H. Paul
dc.contributor.authorWang, Jiang Huai
dc.contributor.authorWang, Jian
dc.contributor.funderNational Natural Science Foundation of Chinaen
dc.contributor.funderNatural Science Foundation of Jiangsu Provinceen
dc.contributor.funderScience and Technology Program of Suzhouen
dc.contributor.funderPediatric Solid Tumor Multidisciplinary Teamen
dc.contributor.funderPediatric Precise Surgical Clinical Medical Center of Suzhouen
dc.date.accessioned2019-06-24T08:52:50Z
dc.date.available2019-06-24T08:52:50Z
dc.date.issued2019-01-14
dc.description.abstractThe detection of microbial pathogens relies on the recognition of highly conserved microbial structures by the membrane sensor Toll-like receptors (TLRs) and cytosolic sensor NOD-like receptors (NLRs). Upon detection, these sensors trigger innate immune responses to eradicate the invaded microbial pathogens. However, it is unclear whether TLR and NOD signaling are both critical for innate immunity to initiate inflammatory and antimicrobial responses against microbial infection. Here we report that activation of both TLR and NOD signaling resulted in an augmented inflammatory response and the crosstalk between TLR and NOD led to an amplified downstream NF-kB activation with increased nuclear transactivation of p65 at TNF-a and IL-6 promoters. Furthermore, co-stimulation of macrophages with TLR and NOD agonists maximized antimicrobial activity with accelerated phagosome maturation. Importantly, administration of both TLR and NOD agonists protected mice against polymicrobial sepsis-associated lethality with increased serum levels of inflammatory cytokines and accelerated bacterial clearance from the circulation and visceral organs. These results demonstrate that activation of both TLR and NOD signaling synergizes to induce efficient inflammatory and antimicrobial responses, thus conferring protection against microbial infection.en
dc.description.sponsorshipNational Natural Science Foundation of China (Grant 81420108022, 81671967, 81501703, 81871594, 31670853, and 81571551); Natural Science Foundation of Jiangsu Province (BK20150294,BK20151206); Science and Technology Program of Suzhou (SYS201555, SYS2018067); Pediatric Solid Tumor Multidisciplinary Team (SZYJTD201706); Pediatric Precise Surgical Clinical Medical Center of Suzhou (SZZXJ201505)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleid3082en
dc.identifier.citationZhou, H., Coveney, A.P., Wu, M., Huang, J., Blankson, S., Zhao, H., O'Leary, D.P., Bai, Z., Li, Y., Redmond, H.P. and Wang, J.H., 2018. Activation of both TLR and NOD signaling confers host innate immunity-mediated protection against microbial infection. Frontiers in immunology, 9:3082. (14pp) DOI: 10.3389/fimmu.2018.03082en
dc.identifier.doi10.3389/fimmu.2018.03082en
dc.identifier.endpage15en
dc.identifier.issn1664-3224
dc.identifier.issued3082en
dc.identifier.journaltitleFrontiers in Immunologyen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/8085
dc.identifier.volume9en
dc.language.isoenen
dc.publisherFrontiers Mediaen
dc.relation.urihttps://www.frontiersin.org/articles/10.3389/fimmu.2018.03082/full
dc.rights© 2019 Zhou, Coveney, Wu, Huang, Blankson, Zhao, O'Leary, Bai, Li, Redmond, Wang and Wangen
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectTLR signalingen
dc.subjectNOD signalingen
dc.subjectInflammatory responseen
dc.subjectAntimicrobila activityen
dc.subjectNF-kappaB pathwayen
dc.subjectPhagosome maturationen
dc.subjectMicrobial infectionen
dc.titleActivation of both TLR and NOD signaling confers host innate immunity-mediated protection against microbial infectionen
dc.typeArticle (peer-reviewed)en
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