Dissecting disease tolerance in Plasmodium vivax malaria using the systemic degree of inflammatory perturbation
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2021 |
| Outros Autores: | , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/50243 |
Resumo: | Financiadora de Estudos e Projetos (FINEP) (grant ward number: 010409605) / Fundo Nacional de Desenvolvimento Cientı´fico e Tecnolo´gico (FNDCTCT- Amazoˆnia), Brazil (M.B.-N.). This study was also financed in part by Coordenacão de Aperfeic¸oamento de Pessoal de Nı´vel Superior (CAPES) (Finance Code 001), Brazil (B.B.A. and M. A.-P.). B.B.A. was supported by a grant from the National Institutes of Health (NIH U01AI115940). The work of K.F.F. was supported by CAPES. C.L.V received a fellowship from Conselho Nacional de Desenvolvimento Cientı´fico e Tecnolo´gico (CNPq). T.A.C. is a scientific initiation fellow from Fundacão de Amparo à Pesquisa do Estado da Bahia (FAPESB). M.B.A. received a fellowship from the FAPESB. BBA, MBN and MVGL are investigators from CNPq (senior fellowship). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
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Vinhaes, Caian L.Carmo, Thomas A.Queiroz, Artur Trancoso LupoFukutani, Kiyoshi FerreiraPereira, Mariana AraújoArriaga, Marıa B.Lacerda, Marcus V. G.Barral Netto, ManoelAndrade, Bruno de Bezerril2021-12-09T14:34:51Z2021-12-09T14:34:51Z2021VINHAES, Caian L. et al. Dissecting disease tolerance in Plasmodium vivax malaria using the systemic degree of inflammatory perturbation. PLoS Neglected Tropical Diseases , 2021.1935-2735https://www.arca.fiocruz.br/handle/icict/5024310.1371/journal.pntd.0009886Financiadora de Estudos e Projetos (FINEP) (grant ward number: 010409605) / Fundo Nacional de Desenvolvimento Cientı´fico e Tecnolo´gico (FNDCTCT- Amazoˆnia), Brazil (M.B.-N.). This study was also financed in part by Coordenacão de Aperfeic¸oamento de Pessoal de Nı´vel Superior (CAPES) (Finance Code 001), Brazil (B.B.A. and M. A.-P.). B.B.A. was supported by a grant from the National Institutes of Health (NIH U01AI115940). The work of K.F.F. was supported by CAPES. C.L.V received a fellowship from Conselho Nacional de Desenvolvimento Cientı´fico e Tecnolo´gico (CNPq). T.A.C. is a scientific initiation fellow from Fundacão de Amparo à Pesquisa do Estado da Bahia (FAPESB). M.B.A. received a fellowship from the FAPESB. BBA, MBN and MVGL are investigators from CNPq (senior fellowship). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative, Salvador, Brazil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative, Salvador, Brazil / Universidade Salvador. Laureate Universities. Curso de Medicina. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative, Salvador, Brazil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative, Salvador, Brazil / Centro Universitário Facultade de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative, Salvador, Brazil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative, Salvador, Brazil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil.Fundação de Medicina Tropical Dr Heitor Vieira Dourado. Instituto de Pesquisa Clínica Carlos Borborema. Manaus, AM, Brasil / Fundação Oswaldo Cruz. Instituto Leônidas & Maria Deane. Manaus, AM, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Instituto Nacional de Ciência e Tecnologia. Instituto de Investigação em Imunologia. São Paulo, SP, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative, Salvador, Brazil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil / Universidade Salvador. Laureate Universities. Curso de Medicina. Salvador, BA, Brasil / Centro Universitário Faculdade de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil.Homeostatic perturbation caused by infection fosters two major defense strategies, resistance and tolerance, which promote the host’s survival. Resistance relates to the ability of the host to restrict the pathogen load. Tolerance minimizes collateral tissue damage without directly affecting pathogen fitness. These concepts have been explored mechanistically in murine models of malaria but only superficially in human disease. Indeed, individuals infected with Plasmodium vivax may present with asymptomatic malaria, only mild symptoms, or be severely ill. We and others have reported a diverse repertoire of immunopathological events that potentially underly susceptibility to disease severity in vivax malaria. Nevertheless, the combined epidemiologic, clinical, parasitological, and immunologic features associated with defining the disease outcomes are still not fully understood. In the present study, we perform an extensive outlining of cytokines and inflammatory proteins in plasma samples from a cohort of individuals from the Brazilian Amazon infected with P. vivax and presenting with asymptomatic (n = 108) or symptomatic (n = 134) disease (106 with mild presentation and 28 with severe malaria), as well as from uninfected endemic controls (n = 128) to elucidate these gaps further. We employ highly multidimensional Systems Immunology analyses using the molecular degree of perturbation to reveal nuances of a unique profile of systemic inflammation and imbalanced immune activation directly linked to disease severity as well as with other clinical and epidemiologic characteristics. Additionally, our findings reveal that the main factor associated with severe cases of P. vivax infection was the number of symptoms, despite of a lower global inflammatory perturbation and parasitemia. In these participants, the number of symptoms directly correlated with perturbation of markers of inflammation and tissue damage. On the other hand, the main factor associated with non-severe infections was the parasitemia values, that correlated only with perturbation of inflammatory markers, such as IL-4 and IL-1β, with a relatively lower number of symptoms. These observations suggest that some persons present severe vivax regardless of pathogen burden and global inflammatory perturbation. Such patients are thus little tolerant to P. vivax infection and show higher susceptibility to disrupt homeostasis and consequently exhibit more clinical manifestations. Other persons are capable to tolerate higher parasitemia with lower inflammatory perturbation and fewer symptoms, developing nonsevere malaria. The analytical approach presented here has capability to define in more details the determinants of disease tolerance in vivax malaria.engPublic Library of SciencePlasmodium vivaxMaláriaInflamaçãoParasitemiaPlasmodium vivaxMaláriaInflammationParasitemiaDissecting disease tolerance in Plasmodium vivax malaria using the systemic degree of inflammatory perturbationinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83097https://www.arca.fiocruz.br/bitstream/icict/50243/1/license.txt36b51ef91c52b5338d9d29ba0cc807bcMD51ORIGINALVinhaes, Caian L. Dissecting....pdfVinhaes, Caian L. Dissecting....pdfapplication/pdf4845939https://www.arca.fiocruz.br/bitstream/icict/50243/2/Vinhaes%2c%20Caian%20L.%20Dissecting....pdfd21e07cb4f895010cfd39d01226ea0e5MD52icict/502432023-03-15 14:34:32.138oai:www.arca.fiocruz.br:icict/50243Q0VTU8ODTyBOw4NPIEVYQ0xVU0lWQSBERSBESVJFSVRPUyBBVVRPUkFJUw0KDQpBbmEgTWFyaWEgRmlzY2luYSBTYW1wYWlvLCBDUEY6IDA2NS40MzEuMDM1LTE1LCB2aW5jdWxhZG8gYSBDUHFHTSAtIENlbnRybyBkZSBQZXNxdWlzYXMgR29uw6dhbG8gTW9uaXoKCkFvIGFjZWl0YXIgb3MgVEVSTU9TIGUgQ09OREnDh8OVRVMgZGVzdGEgQ0VTU8ODTywgbyBBVVRPUiBlL291IFRJVFVMQVIgZGUgZGlyZWl0b3MKYXV0b3JhaXMgc29icmUgYSBPQlJBIGRlIHF1ZSB0cmF0YSBlc3RlIGRvY3VtZW50bzoKCigxKSBDRURFIGUgVFJBTlNGRVJFLCB0b3RhbCBlIGdyYXR1aXRhbWVudGUsIMOgIEZJT0NSVVogLSBGVU5EQcOHw4NPIE9TV0FMRE8gQ1JVWiwgZW0KY2Fyw6F0ZXIgcGVybWFuZW50ZSwgaXJyZXZvZ8OhdmVsIGUgTsODTyBFWENMVVNJVk8sIHRvZG9zIG9zIGRpcmVpdG9zIHBhdHJpbW9uaWFpcyBOw4NPCkNPTUVSQ0lBSVMgZGUgdXRpbGl6YcOnw6NvIGRhIE9CUkEgYXJ0w61zdGljYSBlL291IGNpZW50w61maWNhIGluZGljYWRhIGFjaW1hLCBpbmNsdXNpdmUgb3MgZGlyZWl0b3MKZGUgdm96IGUgaW1hZ2VtIHZpbmN1bGFkb3Mgw6AgT0JSQSwgZHVyYW50ZSB0b2RvIG8gcHJhem8gZGUgZHVyYcOnw6NvIGRvcyBkaXJlaXRvcyBhdXRvcmFpcywgZW0KcXVhbHF1ZXIgaWRpb21hIGUgZW0gdG9kb3Mgb3MgcGHDrXNlczsKCigyKSBBQ0VJVEEgcXVlIGEgY2Vzc8OjbyB0b3RhbCBuw6NvIGV4Y2x1c2l2YSwgcGVybWFuZW50ZSBlIGlycmV2b2fDoXZlbCBkb3MgZGlyZWl0b3MgYXV0b3JhaXMKcGF0cmltb25pYWlzIG7Do28gY29tZXJjaWFpcyBkZSB1dGlsaXphw6fDo28gZGUgcXVlIHRyYXRhIGVzdGUgZG9jdW1lbnRvIGluY2x1aSwgZXhlbXBsaWZpY2F0aXZhbWVudGUsCm9zIGRpcmVpdG9zIGRlIGRpc3BvbmliaWxpemHDp8OjbyBlIGNvbXVuaWNhw6fDo28gcMO6YmxpY2EgZGEgT0JSQSwgZW0gcXVhbHF1ZXIgbWVpbyBvdSB2ZcOtY3VsbywKaW5jbHVzaXZlIGVtIFJlcG9zaXTDs3Jpb3MgRGlnaXRhaXMsIGJlbSBjb21vIG9zIGRpcmVpdG9zIGRlIHJlcHJvZHXDp8OjbywgZXhpYmnDp8OjbywgZXhlY3XDp8OjbywKZGVjbGFtYcOnw6NvLCByZWNpdGHDp8OjbywgZXhwb3Npw6fDo28sIGFycXVpdmFtZW50bywgaW5jbHVzw6NvIGVtIGJhbmNvIGRlIGRhZG9zLCBwcmVzZXJ2YcOnw6NvLCBkaWZ1c8OjbywKZGlzdHJpYnVpw6fDo28sIGRpdnVsZ2HDp8OjbywgZW1wcsOpc3RpbW8sIHRyYWR1w6fDo28sIGR1YmxhZ2VtLCBsZWdlbmRhZ2VtLCBpbmNsdXPDo28gZW0gbm92YXMgb2JyYXMgb3UKY29sZXTDom5lYXMsIHJldXRpbGl6YcOnw6NvLCBlZGnDp8OjbywgcHJvZHXDp8OjbyBkZSBtYXRlcmlhbCBkaWTDoXRpY28gZSBjdXJzb3Mgb3UgcXVhbHF1ZXIgZm9ybWEgZGUKdXRpbGl6YcOnw6NvIG7Do28gY29tZXJjaWFsOwoKKDMpIFJFQ09OSEVDRSBxdWUgYSBjZXNzw6NvIGFxdWkgZXNwZWNpZmljYWRhIGNvbmNlZGUgw6AgRklPQ1JVWiAtIEZVTkRBw4fDg08gT1NXQUxETwpDUlVaIG8gZGlyZWl0byBkZSBhdXRvcml6YXIgcXVhbHF1ZXIgcGVzc29hIOKAkyBmw61zaWNhIG91IGp1csOtZGljYSwgcMO6YmxpY2Egb3UgcHJpdmFkYSwgbmFjaW9uYWwgb3UKZXN0cmFuZ2VpcmEg4oCTIGEgYWNlc3NhciBlIHV0aWxpemFyIGFtcGxhbWVudGUgYSBPQlJBLCBzZW0gZXhjbHVzaXZpZGFkZSwgcGFyYSBxdWFpc3F1ZXIKZmluYWxpZGFkZXMgbsOjbyBjb21lcmNpYWlzOwoKKDQpIERFQ0xBUkEgcXVlIGEgb2JyYSDDqSBjcmlhw6fDo28gb3JpZ2luYWwgZSBxdWUgw6kgbyB0aXR1bGFyIGRvcyBkaXJlaXRvcyBhcXVpIGNlZGlkb3MgZSBhdXRvcml6YWRvcywKcmVzcG9uc2FiaWxpemFuZG8tc2UgaW50ZWdyYWxtZW50ZSBwZWxvIGNvbnRlw7pkbyBlIG91dHJvcyBlbGVtZW50b3MgcXVlIGZhemVtIHBhcnRlIGRhIE9CUkEsCmluY2x1c2l2ZSBvcyBkaXJlaXRvcyBkZSB2b3ogZSBpbWFnZW0gdmluY3VsYWRvcyDDoCBPQlJBLCBvYnJpZ2FuZG8tc2UgYSBpbmRlbml6YXIgdGVyY2Vpcm9zIHBvcgpkYW5vcywgYmVtIGNvbW8gaW5kZW5pemFyIGUgcmVzc2FyY2lyIGEgRklPQ1JVWiAtIEZVTkRBw4fDg08gT1NXQUxETyBDUlVaIGRlCmV2ZW50dWFpcyBkZXNwZXNhcyBxdWUgdmllcmVtIGEgc3Vwb3J0YXIsIGVtIHJhesOjbyBkZSBxdWFscXVlciBvZmVuc2EgYSBkaXJlaXRvcyBhdXRvcmFpcyBvdQpkaXJlaXRvcyBkZSB2b3ogb3UgaW1hZ2VtLCBwcmluY2lwYWxtZW50ZSBubyBxdWUgZGl6IHJlc3BlaXRvIGEgcGzDoWdpbyBlIHZpb2xhw6fDtWVzIGRlIGRpcmVpdG9zOwoKKDUpIEFGSVJNQSBxdWUgY29uaGVjZSBhIFBvbMOtdGljYSBJbnN0aXR1Y2lvbmFsIGRlIEFjZXNzbyBBYmVydG8gZGEgRklPQ1JVWiAtIEZVTkRBw4fDg08KT1NXQUxETyBDUlVaIGUgYXMgZGlyZXRyaXplcyBwYXJhIG8gZnVuY2lvbmFtZW50byBkbyByZXBvc2l0w7NyaW8gaW5zdGl0dWNpb25hbCBBUkNBLgoKQSBQb2zDrXRpY2EgSW5zdGl0dWNpb25hbCBkZSBBY2Vzc28gQWJlcnRvIGRhIEZJT0NSVVogLSBGVU5EQcOHw4NPIE9TV0FMRE8gQ1JVWiByZXNlcnZhCmV4Y2x1c2l2YW1lbnRlIGFvIEFVVE9SIG9zIGRpcmVpdG9zIG1vcmFpcyBlIG9zIHVzb3MgY29tZXJjaWFpcyBzb2JyZSBhcyBvYnJhcyBkZSBzdWEgYXV0b3JpYQplL291IHRpdHVsYXJpZGFkZSwgc2VuZG8gb3MgdGVyY2Vpcm9zIHVzdcOhcmlvcyByZXNwb25zw6F2ZWlzIHBlbGEgYXRyaWJ1acOnw6NvIGRlIGF1dG9yaWEgZSBtYW51dGVuw6fDo28KZGEgaW50ZWdyaWRhZGUgZGEgT0JSQSBlbSBxdWFscXVlciB1dGlsaXphw6fDo28uCgpBIFBvbMOtdGljYSBJbnN0aXR1Y2lvbmFsIGRlIEFjZXNzbyBBYmVydG8gZGEgRklPQ1JVWiAtIEZVTkRBw4fDg08gT1NXQUxETyBDUlVaCnJlc3BlaXRhIG9zIGNvbnRyYXRvcyBlIGFjb3Jkb3MgcHJlZXhpc3RlbnRlcyBkb3MgQXV0b3JlcyBjb20gdGVyY2Vpcm9zLCBjYWJlbmRvIGFvcyBBdXRvcmVzCmluZm9ybWFyIMOgIEluc3RpdHVpw6fDo28gYXMgY29uZGnDp8O1ZXMgZSBvdXRyYXMgcmVzdHJpw6fDtWVzIGltcG9zdGFzIHBvciBlc3RlcyBpbnN0cnVtZW50b3MuCg==Repositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-03-15T17:34:32Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
| dc.title.pt_BR.fl_str_mv |
Dissecting disease tolerance in Plasmodium vivax malaria using the systemic degree of inflammatory perturbation |
| title |
Dissecting disease tolerance in Plasmodium vivax malaria using the systemic degree of inflammatory perturbation |
| spellingShingle |
Dissecting disease tolerance in Plasmodium vivax malaria using the systemic degree of inflammatory perturbation Vinhaes, Caian L. Plasmodium vivax Malária Inflamação Parasitemia Plasmodium vivax Malária Inflammation Parasitemia |
| title_short |
Dissecting disease tolerance in Plasmodium vivax malaria using the systemic degree of inflammatory perturbation |
| title_full |
Dissecting disease tolerance in Plasmodium vivax malaria using the systemic degree of inflammatory perturbation |
| title_fullStr |
Dissecting disease tolerance in Plasmodium vivax malaria using the systemic degree of inflammatory perturbation |
| title_full_unstemmed |
Dissecting disease tolerance in Plasmodium vivax malaria using the systemic degree of inflammatory perturbation |
| title_sort |
Dissecting disease tolerance in Plasmodium vivax malaria using the systemic degree of inflammatory perturbation |
| author |
Vinhaes, Caian L. |
| author_facet |
Vinhaes, Caian L. Carmo, Thomas A. Queiroz, Artur Trancoso Lupo Fukutani, Kiyoshi Ferreira Pereira, Mariana Araújo Arriaga, Marıa B. Lacerda, Marcus V. G. Barral Netto, Manoel Andrade, Bruno de Bezerril |
| author_role |
author |
| author2 |
Carmo, Thomas A. Queiroz, Artur Trancoso Lupo Fukutani, Kiyoshi Ferreira Pereira, Mariana Araújo Arriaga, Marıa B. Lacerda, Marcus V. G. Barral Netto, Manoel Andrade, Bruno de Bezerril |
| author2_role |
author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Vinhaes, Caian L. Carmo, Thomas A. Queiroz, Artur Trancoso Lupo Fukutani, Kiyoshi Ferreira Pereira, Mariana Araújo Arriaga, Marıa B. Lacerda, Marcus V. G. Barral Netto, Manoel Andrade, Bruno de Bezerril |
| dc.subject.other.pt_BR.fl_str_mv |
Plasmodium vivax Malária Inflamação Parasitemia |
| topic |
Plasmodium vivax Malária Inflamação Parasitemia Plasmodium vivax Malária Inflammation Parasitemia |
| dc.subject.en.pt_BR.fl_str_mv |
Plasmodium vivax Malária Inflammation Parasitemia |
| description |
Financiadora de Estudos e Projetos (FINEP) (grant ward number: 010409605) / Fundo Nacional de Desenvolvimento Cientı´fico e Tecnolo´gico (FNDCTCT- Amazoˆnia), Brazil (M.B.-N.). This study was also financed in part by Coordenacão de Aperfeic¸oamento de Pessoal de Nı´vel Superior (CAPES) (Finance Code 001), Brazil (B.B.A. and M. A.-P.). B.B.A. was supported by a grant from the National Institutes of Health (NIH U01AI115940). The work of K.F.F. was supported by CAPES. C.L.V received a fellowship from Conselho Nacional de Desenvolvimento Cientı´fico e Tecnolo´gico (CNPq). T.A.C. is a scientific initiation fellow from Fundacão de Amparo à Pesquisa do Estado da Bahia (FAPESB). M.B.A. received a fellowship from the FAPESB. BBA, MBN and MVGL are investigators from CNPq (senior fellowship). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
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2021 |
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2021-12-09T14:34:51Z |
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2021-12-09T14:34:51Z |
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2021 |
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VINHAES, Caian L. et al. Dissecting disease tolerance in Plasmodium vivax malaria using the systemic degree of inflammatory perturbation. PLoS Neglected Tropical Diseases , 2021. |
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https://www.arca.fiocruz.br/handle/icict/50243 |
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1935-2735 |
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10.1371/journal.pntd.0009886 |
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VINHAES, Caian L. et al. Dissecting disease tolerance in Plasmodium vivax malaria using the systemic degree of inflammatory perturbation. PLoS Neglected Tropical Diseases , 2021. 1935-2735 10.1371/journal.pntd.0009886 |
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