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Organotypic endothelial adhesion molecules are key for Trypanosoma brucei tropism and virulence

2021Artigo científico Acesso aberto
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dc.contributor.authorDe Niz, Mariana
dc.contributor.authorBrás, Daniela
dc.contributor.authorOuarné, Marie
dc.contributor.authorPedro, Mafalda
dc.contributor.authorNascimento, Ana M.
dc.contributor.authorHenao Mišíková, Lenka
dc.contributor.authorFranco, Claudio
dc.contributor.authorFigueiredo, Luisa M.
dc.date.accessioned2021-09-28T13:27:25Z
dc.date.available2021-09-28T13:27:25Z
dc.date.issued2021
dc.description© 2021 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).pt_PT
dc.description.abstractTrypanosoma brucei is responsible for lethal diseases in humans and cattle in Sub-Saharan Africa. These extracellular parasites extravasate from the blood circulation into several tissues. The importance of the vasculature in tissue tropism is poorly understood. Using intravital imaging and bioluminescence, we observe that gonadal white adipose tissue and pancreas are the two main parasite reservoirs. We show that reservoir establishment happens before vascular permeability is compromised, suggesting that extravasation is an active mechanism. Blocking endothelial surface adhesion molecules (E-selectin, P-selectins, or ICAM2) significantly reduces extravascular parasite density in all organs and delays host lethality. Remarkably, blocking CD36 has a specific effect on adipose tissue tropism that is sufficient to delay lethality, suggesting that establishment of the adipose tissue reservoir is necessary for parasite virulence. This work demonstrates the importance of the vasculature in a T. brucei infection and identifies organ-specific adhesion molecules as key players for tissue tropism.pt_PT
dc.description.sponsorshipThis work was supported by HFSP (LT000047/2019-L) and EMBO (ALTF 1048-2016) to M.D.N. L.M.F. is an Investigator CEEC of the Fundação para a Ciência e a Tecnologia (CEECIND/03322/2108), and the laboratory is funded by ERC (FatTryp, ref. 771714). C.A.F. was supported by a European Research Council starting grant (679368), the Fondation Leducq (17CVD03), and the Fundação para a Ciência e a Tecnologia (grants IF/00412/2012, EXPL/BEX-BCM/2258/2013, PRECISE-LISBOA-01-0145-FEDER-016394, PTDC/MED-PAT/31639/2017, PTDC/BIA-CEL/32180/2017, and CEECIND/04251/2017).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationCell Rep. 2021 Sep 21;36(12):109741pt_PT
dc.identifier.doi10.1016/j.celrep.2021.109741pt_PT
dc.identifier.eissn2639-1856
dc.identifier.issn2211-1247
dc.identifier.urihttp://hdl.handle.net/10451/49658
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationLT000047/2019-Lpt_PT
dc.relationALTF 1048-2016pt_PT
dc.relationCEECIND/03322/2108pt_PT
dc.relation771714pt_PT
dc.relationPRINCIPLES OF AXIAL POLARITY-DRIVEN VASCULAR PATTERNING
dc.relationPRECISE-LISBOA-01-0145-FEDER-016394pt_PT
dc.relationCEECIND/04251/2017pt_PT
dc.relation.publisherversionhttps://www.sciencedirect.com/journal/cell-reportspt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectTrypanosoma bruceipt_PT
dc.subjectEndothelial receptorspt_PT
dc.subjectIntravital microscopypt_PT
dc.subjectParasitespt_PT
dc.subjectTropismpt_PT
dc.subjectVasculaturept_PT
dc.titleOrganotypic endothelial adhesion molecules are key for Trypanosoma brucei tropism and virulencept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitlePRINCIPLES OF AXIAL POLARITY-DRIVEN VASCULAR PATTERNING
oaire.awardURIinfo:eu-repo/grantAgreement/EC/H2020/679368/EU
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/EXPL%2FBEX-BCM%2F2258%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/152869/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/153415/PT
oaire.citation.issue12pt_PT
oaire.citation.titleCell Reportspt_PT
oaire.citation.volume36pt_PT
oaire.fundingStreamH2020
oaire.fundingStream3599-PPCDT
oaire.fundingStream3599-PPCDT
oaire.fundingStream3599-PPCDT
person.familyNameDe Niz
person.familyNameBrás
person.familyNameOuarné
person.familyNamePedro
person.familyNameHenao Mišíková
person.familyNameFranco
person.familyNameFigueiredo
person.givenNameMariana
person.givenNameDaniela
person.givenNameMarie
person.givenNameMafalda
person.givenNameLenka
person.givenNameClaudio
person.givenNameLuisa M
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person.identifier.orcid0000-0002-2667-3962
person.identifier.orcid0000-0003-4724-4363
person.identifier.orcid0000-0001-6441-2416
person.identifier.orcid0000-0002-0992-9946
person.identifier.orcid0000-0002-2861-3883
person.identifier.orcid0000-0002-5752-6586
person.identifier.scopus-author-id57376801800
person.identifier.scopus-author-id24280736600
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameEuropean Commission
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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