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Serotype b of Aggregatibacter actinomycetemcomitans triggers pro-inflammatory responses and amyloid beta secretion in hippocampal cells: a novel link between periodontitis and Alzheimer´s disease?

dc.contributor.authorDíaz-Zúñiga J.
dc.contributor.authorMuñoz Y.
dc.contributor.authorMelgar-Rodríguez S.
dc.contributor.authorMore J.
dc.contributor.authorBruna B.
dc.contributor.authorLobos P.
dc.contributor.authorMonasterio G.
dc.contributor.authorVernal R.
dc.contributor.authorPaula-Lima A.
dc.date.accessioned2020-09-02T22:16:53Z
dc.date.available2020-09-02T22:16:53Z
dc.date.issued2019
dc.identifier10.1080/20002297.2019.1586423
dc.identifier.citation11, 1, -
dc.identifier.issn20002297
dc.identifier.urihttps://hdl.handle.net/20.500.12728/4369
dc.descriptionIntroduction: Previous reports have proposed that Periodontal disease (PDis) predisposes to Alzheimer’s disease (AD), both highly prevalent pathologies among the elderly. The bacteria Aggregatibacter actinomycetemcomitans (Aa), associated with the most aggressive forms of PDis, are classified in different serotypes with distinct virulence according to the antigenicity of their lipopolysaccharide (LPS). Methods: Here, we determined the effects of purified LPS, from serotypes a, b or c of Aa, on primary cultures of microglia or mixed hippocampal cells. Results: We found that both culture types exhibited higher levels of inflammatory cytokines (IL-1β, IL-6 and TNFα) when treated with serotype b-LPS, compared with controls, as quantified by qPCR and/or ELISA. Also, cultures treated with serotype a-LPS displayed increased mRNA levels of the modulatory cytokines IL-4 and IL-10. Mixed hippocampal cultures treated with serotype b-LPS exhibited severe neuronal morphological changes and displayed increased levels of secreted Aβ1-42 peptide. These results indicate that LPS from different Aa serotypes triggers discriminatory immune responses, which differentially affect primary hippocampal cells. Conclusion: Altogether, our results show that treatment with serotype b-LPS triggers the secretion of proinflammatory cytokines by microglia, induces neurite shrinking, and increases the extracellular Aβ1-42 levels, all features strongly associated with the etiology of AD. © 2019, © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
dc.language.isoen
dc.publisherTaylor and Francis Ltd.
dc.subjectAlzheimer´s disease
dc.subjectcytokines
dc.subjectinflammation
dc.subjectmicroglia
dc.subjectneurons
dc.subjectPeriodontitis
dc.subjectamyloid beta protein
dc.subjectamyloid beta protein[1-42]
dc.subjectinterleukin 10
dc.subjectinterleukin 1beta
dc.subjectinterleukin 4
dc.subjectinterleukin 6
dc.subjectlipopolysaccharide
dc.subjectmessenger RNA
dc.subjecttoll like receptor 2
dc.subjecttoll like receptor 4
dc.subjecttumor necrosis factor
dc.subjectAggregatibacter actinomycetemcomitans
dc.subjectAggregatibacter actinomycetemcomitans serotype b
dc.subjectAlzheimer disease
dc.subjectanimal cell
dc.subjectanimal tissue
dc.subjectArticle
dc.subjectbacterial virulence
dc.subjectcellular parameters
dc.subjectcontrolled study
dc.subjectcytokine release
dc.subjectdisease association
dc.subjectembryo
dc.subjectenzyme linked immunosorbent assay
dc.subjectextracellular matrix
dc.subjectfemale
dc.subjectgene expression
dc.subjecthippocampal neuronal culture
dc.subjectimmune response
dc.subjectinflammation
dc.subjectmicroglial cell culture
dc.subjectneurite shrinking
dc.subjectnonhuman
dc.subjectpathogenesis
dc.subjectperiodontitis
dc.subjectpolymerase chain reaction
dc.subjectprotein secretion
dc.subjectrat
dc.titleSerotype b of Aggregatibacter actinomycetemcomitans triggers pro-inflammatory responses and amyloid beta secretion in hippocampal cells: a novel link between periodontitis and Alzheimer´s disease?
dc.typeArticle


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