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dc.contributor.authorAyllon, Nieves
dc.contributor.authorVillar, Margarita
dc.contributor.authorGalindo, Ruth C.
dc.contributor.authorKocan, Katherine M.
dc.contributor.authorSima, Radek
dc.contributor.authorLopez, Juan Antonio 
dc.contributor.authorVazquez, Jesus 
dc.contributor.authorAlberdi, Pilar
dc.contributor.authorCabezas-Cruz, Alejandro
dc.contributor.authorKopacek, Petr
dc.contributor.authorde la Fuente, Jose
dc.date.accessioned2017-11-27T13:49:53Z
dc.date.available2017-11-27T13:49:53Z
dc.date.issued2015
dc.identifierISI:000352197100077
dc.identifier.citationPLoS Genet. 2015; 11(3):e1005120
dc.identifier.issn1553-7404
dc.identifier.urihttp://hdl.handle.net/20.500.12105/5412
dc.description.abstractAnaplasma phagocytophilum is an emerging pathogen that causes human granulocytic anaplasmosis. Infection with this zoonotic pathogen affects cell function in both vertebrate host and the tick vector, Ixodes scapularis. Global tissue-specific response and apoptosis signaling pathways were characterized in I. scapularis nymphs and adult female midguts and salivary glands infected with A. phagocytophilum using a systems biology approach combining transcriptomics and proteomics. Apoptosis was selected for pathway-focused analysis due to its role in bacterial infection of tick cells. The results showed tissue-specific differences in tick response to infection and revealed differentiated regulation of apoptosis pathways. The impact of bacterial infection was more pronounced in tick nymphs and midguts than in salivary glands, probably reflecting bacterial developmental cycle. All apoptosis pathways described in other organisms were identified in I. scapularis, except for the absence of the Perforin ortholog. Functional characterization using RNA interference showed that Porin knockdown significantly increases tick colonization by A. phagocytophilum. Infection with A. phagocytophilum produced complex tissue-specific alterations in transcript and protein levels. In tick nymphs, the results suggested a possible effect of bacterial infection on the inhibition of tick immune response. In tick midguts, the results suggested that A. phagocytophilum infection inhibited cell apoptosis to facilitate and establish infection through up-regulation of the JAK/STAT pathway. Bacterial infection inhibited the intrinsic apoptosis pathway in tick salivary glands by down-regulating Porin expression that resulted in the inhibition of Cytochrome c release as the anti-apoptotic mechanism to facilitate bacterial infection. However, tick salivary glands may promote apoptosis to limit bacterial infection through induction of the extrinsic apoptosis pathway. These dynamic changes in response to A. phagocytophilum in I. scapularis tissue-specific transcriptome and proteome demonstrated the complexity of the tick response to infection and will contribute to characterize gene regulation in ticks.
dc.description.sponsorshipThis research was supported by grants BFU2011-23896, the EU FP7 ANTIGONE project number 278976, the Oklahoma Agricultural Experiment Grant 1669 and the Walter R. Sitlington Endowed Chair for Food Animal Research to KMK. NA and RCG were funded by MEC, Spain. RS was supported by the project Postdok\_BIOGLOBE (CZ.1.07/2.3.00/30.0032) and the Grant 13-12816P (GA CR). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
dc.language.isoeng
dc.publisherPUBLIC LIBRARY SCIENCE
dc.relation.isversionofPublisher's version
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectFATTY-ACID SYNTHASE
dc.subjectGENE-EXPRESSION
dc.subjectQUANTITATIVE PROTEOMICS
dc.subjectHUMAN NEUTROPHILS
dc.subjectCANCER-CELLS
dc.subjectRNA-SEQ
dc.subjectINFECTION
dc.subjectINHIBITORS
dc.subjectLIKELIHOOD
dc.subjectEHRLICHIA
dc.titleSystems Biology of Tissue-Specific Response to Anaplasma phagocytophilum Reveals Differentiated Apoptosis in the Tick Vector Ixodes scapularis
dc.typeArtículo
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID25815810
dc.format.volume11
dc.identifier.doi10.1371/journal.pgen.1005120
dc.contributor.funderEuropean Commission
dc.contributor.funderOklahoma Agricultural Experiment Grant
dc.contributor.funderMinisterio de Economía y Competitividad (España)
dc.description.peerreviewed
dc.relation.publisherversionhttps://doi.org/10.1371/journal.pgen.1005120
dc.identifier.journalPLOS GENETICS
dc.repisalud.orgCNICCNIC::Grupos de investigación::Proteómica cardiovascular
dc.repisalud.orgCNICCNIC::Unidades técnicas::Proteómica / Metabolómica
dc.repisalud.institucionCNIC
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/278976/EUes_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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