Asymptomatic vivax malaria is associated with an IFN-γ-program on adaptive immunity

Abstract The adaptive immunity against Plasmodium vivax is thought to be essential to limit parasite growth during asymptomatic malaria, preventing the occurrence of symptoms. However, the mechanisms governing clinical immunity during asymptomatic infections are not understood. Here, we investigated...

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Main Authors: Gregório Guilherme Almeida, Camila Medeiros Costa, Pedro Augusto Carvalho Costa, Gabriela Ribeiro Gomes, Maria Marta Figueiredo, Katherine Jéssica Torres, Alex Fiorini de Carvalho, Bruno Vinícius Santos Valiate, Julia Ramos Sampaio, Brener Cunha Carvalho, Dhelio Batista Pereira, Alexia Martines, Mauro Shugiro Tada, Irene Silva Soares, Jamie Ponmattam, Marcia Caldas de Castro, Douglas Taylor Golenbock, Ricardo Tostes Gazzinelli, Lis Ribeiro do Valle Antonelli
Format: Article
Language:English
Published: BMC 2025-03-01
Series:Journal of Translational Medicine
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Online Access:https://doi.org/10.1186/s12967-025-06353-1
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author Gregório Guilherme Almeida
Camila Medeiros Costa
Pedro Augusto Carvalho Costa
Gabriela Ribeiro Gomes
Maria Marta Figueiredo
Katherine Jéssica Torres
Alex Fiorini de Carvalho
Bruno Vinícius Santos Valiate
Julia Ramos Sampaio
Brener Cunha Carvalho
Dhelio Batista Pereira
Alexia Martines
Mauro Shugiro Tada
Irene Silva Soares
Jamie Ponmattam
Marcia Caldas de Castro
Douglas Taylor Golenbock
Ricardo Tostes Gazzinelli
Lis Ribeiro do Valle Antonelli
author_facet Gregório Guilherme Almeida
Camila Medeiros Costa
Pedro Augusto Carvalho Costa
Gabriela Ribeiro Gomes
Maria Marta Figueiredo
Katherine Jéssica Torres
Alex Fiorini de Carvalho
Bruno Vinícius Santos Valiate
Julia Ramos Sampaio
Brener Cunha Carvalho
Dhelio Batista Pereira
Alexia Martines
Mauro Shugiro Tada
Irene Silva Soares
Jamie Ponmattam
Marcia Caldas de Castro
Douglas Taylor Golenbock
Ricardo Tostes Gazzinelli
Lis Ribeiro do Valle Antonelli
author_sort Gregório Guilherme Almeida
collection DOAJ
description Abstract The adaptive immunity against Plasmodium vivax is thought to be essential to limit parasite growth during asymptomatic malaria, preventing the occurrence of symptoms. However, the mechanisms governing clinical immunity during asymptomatic infections are not understood. Here, we investigated the adaptive cellular compartment in asymptomatic P. vivax-infected individuals (ASY) compared to symptomatic patients (SY) and healthy donors (CTL). Our integrative analysis revealed a TH1-biased immune signature with expanded populations of TH1 CD4+ T cells associated with the asymptomatic infection. In addition, there is an expanded population of proliferating atypical memory B cells that correlate with IgG levels against P. vivax antigens and parasitemia. The absence of systemic inflammation based on a comprehensive panel of soluble markers and the lower expression of some regulatory markers suggests a controlled inflammatory response that can be derived from an effective control of parasite growth. Our findings suggest that ASY maintain a pool of IFN-γ-associated Th cell phenotypes that orchestrate the immune response, limiting parasitemia and preventing clinical malaria.
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spelling doaj-art-ec2ed447e4bf4d92b798ef1777d3e2cc2025-08-20T03:41:47ZengBMCJournal of Translational Medicine1479-58762025-03-0123111710.1186/s12967-025-06353-1Asymptomatic vivax malaria is associated with an IFN-γ-program on adaptive immunityGregório Guilherme Almeida0Camila Medeiros Costa1Pedro Augusto Carvalho Costa2Gabriela Ribeiro Gomes3Maria Marta Figueiredo4Katherine Jéssica Torres5Alex Fiorini de Carvalho6Bruno Vinícius Santos Valiate7Julia Ramos Sampaio8Brener Cunha Carvalho9Dhelio Batista Pereira10Alexia Martines11Mauro Shugiro Tada12Irene Silva Soares13Jamie Ponmattam14Marcia Caldas de Castro15Douglas Taylor Golenbock16Ricardo Tostes Gazzinelli17Lis Ribeiro do Valle Antonelli18Laboratório de Biologia e Imunologia de Doenças Infecciosas e Parasitárias, Instituto René Rachou/Fiocruz Minas, Minas GeraisLaboratório de Biologia e Imunologia de Doenças Infecciosas e Parasitárias, Instituto René Rachou/Fiocruz Minas, Minas GeraisLaboratório de Biologia e Imunologia de Doenças Infecciosas e Parasitárias, Instituto René Rachou/Fiocruz Minas, Minas GeraisLaboratório de Biologia e Imunologia de Doenças Infecciosas e Parasitárias, Instituto René Rachou/Fiocruz Minas, Minas GeraisLaboratório de Biologia e Imunologia de Doenças Infecciosas e Parasitárias, Instituto René Rachou/Fiocruz Minas, Minas GeraisLaboratorio de Malaria, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano HerediaCT vacinas, Universidade Federal de Minas Gerais e Instituto René Rachou, Fundação Oswaldo Cruz, Minas GeraisLaboratório de Imunopatologia, Instituto René Rachou/Fiocruz MinasLaboratório de Imunopatologia, Instituto René Rachou/Fiocruz MinasLaboratório de Imunopatologia, Instituto René Rachou/Fiocruz MinasAmbulatório de Malária, Centro de Pesquisa em Medicina TropicalAmbulatório de Malária, Centro de Pesquisa em Medicina TropicalAmbulatório de Malária, Centro de Pesquisa em Medicina TropicalDepartamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São PauloDepartment of Global Health and Population, Harvard T.H. Chan School of Public HealthDepartment of Global Health and Population, Harvard T.H. Chan School of Public HealthDivision of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Chan Medical SchoolLaboratório de Imunopatologia, Instituto René Rachou/Fiocruz MinasLaboratório de Biologia e Imunologia de Doenças Infecciosas e Parasitárias, Instituto René Rachou/Fiocruz Minas, Minas GeraisAbstract The adaptive immunity against Plasmodium vivax is thought to be essential to limit parasite growth during asymptomatic malaria, preventing the occurrence of symptoms. However, the mechanisms governing clinical immunity during asymptomatic infections are not understood. Here, we investigated the adaptive cellular compartment in asymptomatic P. vivax-infected individuals (ASY) compared to symptomatic patients (SY) and healthy donors (CTL). Our integrative analysis revealed a TH1-biased immune signature with expanded populations of TH1 CD4+ T cells associated with the asymptomatic infection. In addition, there is an expanded population of proliferating atypical memory B cells that correlate with IgG levels against P. vivax antigens and parasitemia. The absence of systemic inflammation based on a comprehensive panel of soluble markers and the lower expression of some regulatory markers suggests a controlled inflammatory response that can be derived from an effective control of parasite growth. Our findings suggest that ASY maintain a pool of IFN-γ-associated Th cell phenotypes that orchestrate the immune response, limiting parasitemia and preventing clinical malaria.https://doi.org/10.1186/s12967-025-06353-1Plasmodium vivaxAsymptomatic malariaMalariaCD4 T cellsB cells
spellingShingle Gregório Guilherme Almeida
Camila Medeiros Costa
Pedro Augusto Carvalho Costa
Gabriela Ribeiro Gomes
Maria Marta Figueiredo
Katherine Jéssica Torres
Alex Fiorini de Carvalho
Bruno Vinícius Santos Valiate
Julia Ramos Sampaio
Brener Cunha Carvalho
Dhelio Batista Pereira
Alexia Martines
Mauro Shugiro Tada
Irene Silva Soares
Jamie Ponmattam
Marcia Caldas de Castro
Douglas Taylor Golenbock
Ricardo Tostes Gazzinelli
Lis Ribeiro do Valle Antonelli
Asymptomatic vivax malaria is associated with an IFN-γ-program on adaptive immunity
Journal of Translational Medicine
Plasmodium vivax
Asymptomatic malaria
Malaria
CD4 T cells
B cells
title Asymptomatic vivax malaria is associated with an IFN-γ-program on adaptive immunity
title_full Asymptomatic vivax malaria is associated with an IFN-γ-program on adaptive immunity
title_fullStr Asymptomatic vivax malaria is associated with an IFN-γ-program on adaptive immunity
title_full_unstemmed Asymptomatic vivax malaria is associated with an IFN-γ-program on adaptive immunity
title_short Asymptomatic vivax malaria is associated with an IFN-γ-program on adaptive immunity
title_sort asymptomatic vivax malaria is associated with an ifn γ program on adaptive immunity
topic Plasmodium vivax
Asymptomatic malaria
Malaria
CD4 T cells
B cells
url https://doi.org/10.1186/s12967-025-06353-1
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