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The soluble pattern recognition receptor PTX3 links humoral innate and adaptive immune responses by helping marginal zone B cells

dc.contributor.authorChorny, Alejo
dc.contributor.authorCasas-Recasens, Sandra
dc.contributor.authorSintes, Jordi
dc.contributor.authorShan, Meimei
dc.contributor.authorPolentarutti, Nadia
dc.contributor.authorGarcía-Escudero, Ramón
dc.contributor.authorWalland, A. Cooper
dc.contributor.authorYeiser, John R.
dc.contributor.authorCassis, Linda
dc.contributor.authorCarrillo, Jorge
dc.contributor.authorPuga, Irene
dc.contributor.authorCunha, Cristina
dc.contributor.authorBastos, Hélder
dc.contributor.authorRodrigues, Fernando
dc.contributor.authorLacerda, João
dc.contributor.authorMorais, António
dc.contributor.authorDieguez-Gonzalez, Rebeca
dc.contributor.authorHeeger, Peter S.
dc.contributor.authorSalvatori, Giovanni
dc.contributor.authorCarvalho, Agostinho
dc.contributor.authorGarcia-Sastre, Adolfo
dc.contributor.authorBlander, J. Magarian
dc.contributor.authorMantovani, Alberto
dc.contributor.authorGarlanda, Cecilia
dc.contributor.authorCerutti, Andrea
dc.date.accessioned2022-11-25T15:39:00Z
dc.date.available2022-11-25T15:39:00Z
dc.date.issued2016
dc.description© 2016 Chorny et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).pt_PT
dc.description.abstractPentraxin 3 (PTX3) is a fluid-phase pattern recognition receptor of the humoral innate immune system with ancestral antibody-like properties but unknown antibody-inducing function. In this study, we found binding of PTX3 to splenic marginal zone (MZ) B cells, an innate-like subset of antibody-producing lymphocytes strategically positioned at the interface between the circulation and the adaptive immune system. PTX3 was released by a subset of neutrophils that surrounded the splenic MZ and expressed an immune activation-related gene signature distinct from that of circulating neutrophils. Binding of PTX3 promoted homeostatic production of IgM and class-switched IgG antibodies to microbial capsular polysaccharides, which decreased in PTX3-deficient mice and humans. In addition, PTX3 increased IgM and IgG production after infection with blood-borne encapsulated bacteria or immunization with bacterial carbohydrates. This immunogenic effect stemmed from the activation of MZ B cells through a neutrophil-regulated pathway that elicited class switching and plasmablast expansion via a combination of T cell-independent and T cell-dependent signals. Thus, PTX3 may bridge the humoral arms of the innate and adaptive immune systems by serving as an endogenous adjuvant for MZ B cells. This property could be harnessed to develop more effective vaccines against encapsulated pathogens.pt_PT
dc.description.sponsorshipThis study was supported by European Advanced grant ERC-2011-ADG-20110310, Ministerio de Ciencia e Innovación grant SAF2011-25241, and Marie Curie reintegration grant PIRG-08-GA-2010-276928 to A. Cerutti; Sara Borrell post-doctoral fellowships to A. Chorny; and US National Institutes of Health grants R01 AI57653, U01 AI95613, P01 AI61093, and U19 096187 to A. Cerutti. C. Cunha and A. Carvalho were funded by grants from Fundação para a Ciência e Tecnologia, co-funded by Programa Operacional Regional do Norte (ON.2—O Novo Norte)., and from the Quadro de Referência Estratégico Nacional (SFRH/BPD/96176/2013 to C. Cunha and grant IF/00735/2014 to A. Carvalho) through the Fundo Europeu de Desenvolvimento Regional and Projeto Estratégico (LA 26 – 2013–2014; PEst-C/SAU/LA0026/2013). The financial support of the European Commission (FP7-HEALTH-2011-ADITEC-No.280873 and ERC-PHII-669415) to A. Mantovani is gratefully acknowledged.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationJ Exp Med. 2016 Sep 19;213(10):2167-2185pt_PT
dc.identifier.doi10.1084/jem.20150282pt_PT
dc.identifier.eissn1540-9538
dc.identifier.issn0022-1007
dc.identifier.urihttp://hdl.handle.net/10451/55249
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherRockefeller University Presspt_PT
dc.relationERC-2011-ADG-20110310pt_PT
dc.relationSAF2011-25241pt_PT
dc.relationTHE ROLE OF INFLAMMASOME ACTIVATION IN HOST IMMUNITY TO FUNGAL INFECTION - The inflammasome-microbiota interplay in antifungal immunity
dc.relation2013 - Strategic Project
dc.relationERC-PHII-669415pt_PT
dc.relationAdvanced Immunization Technologies
dc.relation.publisherversionhttps://rupress.org/jempt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/pt_PT
dc.titleThe soluble pattern recognition receptor PTX3 links humoral innate and adaptive immune responses by helping marginal zone B cellspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleTHE ROLE OF INFLAMMASOME ACTIVATION IN HOST IMMUNITY TO FUNGAL INFECTION - The inflammasome-microbiota interplay in antifungal immunity
oaire.awardTitle2013 - Strategic Project
oaire.awardTitleAdvanced Immunization Technologies
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBPD%2F96176%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/Investigador FCT/IF%2F00735%2F2014%2FCP1212%2FCT0001/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6820 - DCRRNI ID/PEst-C%2FSAU%2FLA0026%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/EC/FP7/280873/EU
oaire.citation.endPage2185pt_PT
oaire.citation.issue10pt_PT
oaire.citation.startPage2167pt_PT
oaire.citation.titleJournal of Experimental Medicinept_PT
oaire.citation.volume213pt_PT
oaire.fundingStreamInvestigador FCT
oaire.fundingStream6820 - DCRRNI ID
oaire.fundingStreamFP7
person.familyNameLacerda
person.givenNameJoão
person.identifier559297
person.identifier.ciencia-id6412-2B63-2364
person.identifier.orcid0000-0003-1351-2809
person.identifier.scopus-author-id6603819609
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.identifierhttp://doi.org/10.13039/501100008530
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
project.funder.nameEuropean Commission
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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