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Gene Signatures of Symptomatic and Asymptomatic Clinical-Immunological Profiles of Human Infection by Leishmania (L.) chagasi in Amazonian Brazil

Individuals infected with Leishmania (L.) chagasi may present different asymptomatic and symptomatic stages of infection, which vary in the clinical–immunological profiles that can be classified as asymptomatic infection (AI), subclinical resistant infection (SRI), indeterminate initial infection (I...

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Autores principales: da Matta, Vania Lucia R., Gonçalves, André N., Gomes, Cláudia Maria C., Chouman, Islam H., Ferreira, Frederico M., Campos, Marliane B., Lima, Luciana V., Vasconcelos dos Santos, Thiago, Ramos, Patrícia Karla, Furtado, Rodrigo R., Laurenti, Marcia D., Corbett, Carlos Eduardo P., Nakaya, Helder I., Silveira, Fernando T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10058599/
https://www.ncbi.nlm.nih.gov/pubmed/36985226
http://dx.doi.org/10.3390/microorganisms11030653
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author da Matta, Vania Lucia R.
Gonçalves, André N.
Gomes, Cláudia Maria C.
Chouman, Islam H.
Ferreira, Frederico M.
Campos, Marliane B.
Lima, Luciana V.
Vasconcelos dos Santos, Thiago
Ramos, Patrícia Karla
Furtado, Rodrigo R.
Laurenti, Marcia D.
Corbett, Carlos Eduardo P.
Nakaya, Helder I.
Silveira, Fernando T.
author_facet da Matta, Vania Lucia R.
Gonçalves, André N.
Gomes, Cláudia Maria C.
Chouman, Islam H.
Ferreira, Frederico M.
Campos, Marliane B.
Lima, Luciana V.
Vasconcelos dos Santos, Thiago
Ramos, Patrícia Karla
Furtado, Rodrigo R.
Laurenti, Marcia D.
Corbett, Carlos Eduardo P.
Nakaya, Helder I.
Silveira, Fernando T.
author_sort da Matta, Vania Lucia R.
collection PubMed
description Individuals infected with Leishmania (L.) chagasi may present different asymptomatic and symptomatic stages of infection, which vary in the clinical–immunological profiles that can be classified as asymptomatic infection (AI), subclinical resistant infection (SRI), indeterminate initial infection (III), subclinical oligosymptomatic infection (SOI), and symptomatic infection (SI) (=American visceral leishmaniasis, AVL). However, little is known about the molecular differences between individuals having each profile. Here, we performed whole-blood transcriptomic analyses of 56 infected individuals from Pará State (Brazilian Amazon), covering all five profiles. We then identified the gene signatures of each profile by comparing their transcriptome with those of 11 healthy individuals from the same area. Symptomatic individuals with SI (=AVL) and SOI profiles showed higher transcriptome perturbation when compared to those asymptomatic III, AI and SRI profiles, suggesting that disease severity may be associated with greater transcriptomic changes. Although the expression of many genes was altered on each profile, very few genes were shared among the profiles. This indicated that each profile has a unique gene signature. The innate immune system pathway was strongly activated only in asymptomatic AI and SRI profiles, suggesting the control of infection. In turn, pathways such as MHC Class II antigen presentation and NF-kB activation in B cells seemed to be specifically induced in symptomatic SI (=AVL) and SOI profiles. Moreover, cellular response to starvation was down-regulated in those symptomatic profiles. Overall, this study revealed five distinct transcriptional patterns associated to the clinical–immunological (symptomatic and asymptomatic) profiles of human L. (L.) chagasi-infection in the Brazilian Amazon.
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spelling pubmed-100585992023-03-30 Gene Signatures of Symptomatic and Asymptomatic Clinical-Immunological Profiles of Human Infection by Leishmania (L.) chagasi in Amazonian Brazil da Matta, Vania Lucia R. Gonçalves, André N. Gomes, Cláudia Maria C. Chouman, Islam H. Ferreira, Frederico M. Campos, Marliane B. Lima, Luciana V. Vasconcelos dos Santos, Thiago Ramos, Patrícia Karla Furtado, Rodrigo R. Laurenti, Marcia D. Corbett, Carlos Eduardo P. Nakaya, Helder I. Silveira, Fernando T. Microorganisms Article Individuals infected with Leishmania (L.) chagasi may present different asymptomatic and symptomatic stages of infection, which vary in the clinical–immunological profiles that can be classified as asymptomatic infection (AI), subclinical resistant infection (SRI), indeterminate initial infection (III), subclinical oligosymptomatic infection (SOI), and symptomatic infection (SI) (=American visceral leishmaniasis, AVL). However, little is known about the molecular differences between individuals having each profile. Here, we performed whole-blood transcriptomic analyses of 56 infected individuals from Pará State (Brazilian Amazon), covering all five profiles. We then identified the gene signatures of each profile by comparing their transcriptome with those of 11 healthy individuals from the same area. Symptomatic individuals with SI (=AVL) and SOI profiles showed higher transcriptome perturbation when compared to those asymptomatic III, AI and SRI profiles, suggesting that disease severity may be associated with greater transcriptomic changes. Although the expression of many genes was altered on each profile, very few genes were shared among the profiles. This indicated that each profile has a unique gene signature. The innate immune system pathway was strongly activated only in asymptomatic AI and SRI profiles, suggesting the control of infection. In turn, pathways such as MHC Class II antigen presentation and NF-kB activation in B cells seemed to be specifically induced in symptomatic SI (=AVL) and SOI profiles. Moreover, cellular response to starvation was down-regulated in those symptomatic profiles. Overall, this study revealed five distinct transcriptional patterns associated to the clinical–immunological (symptomatic and asymptomatic) profiles of human L. (L.) chagasi-infection in the Brazilian Amazon. MDPI 2023-03-03 /pmc/articles/PMC10058599/ /pubmed/36985226 http://dx.doi.org/10.3390/microorganisms11030653 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
da Matta, Vania Lucia R.
Gonçalves, André N.
Gomes, Cláudia Maria C.
Chouman, Islam H.
Ferreira, Frederico M.
Campos, Marliane B.
Lima, Luciana V.
Vasconcelos dos Santos, Thiago
Ramos, Patrícia Karla
Furtado, Rodrigo R.
Laurenti, Marcia D.
Corbett, Carlos Eduardo P.
Nakaya, Helder I.
Silveira, Fernando T.
Gene Signatures of Symptomatic and Asymptomatic Clinical-Immunological Profiles of Human Infection by Leishmania (L.) chagasi in Amazonian Brazil
title Gene Signatures of Symptomatic and Asymptomatic Clinical-Immunological Profiles of Human Infection by Leishmania (L.) chagasi in Amazonian Brazil
title_full Gene Signatures of Symptomatic and Asymptomatic Clinical-Immunological Profiles of Human Infection by Leishmania (L.) chagasi in Amazonian Brazil
title_fullStr Gene Signatures of Symptomatic and Asymptomatic Clinical-Immunological Profiles of Human Infection by Leishmania (L.) chagasi in Amazonian Brazil
title_full_unstemmed Gene Signatures of Symptomatic and Asymptomatic Clinical-Immunological Profiles of Human Infection by Leishmania (L.) chagasi in Amazonian Brazil
title_short Gene Signatures of Symptomatic and Asymptomatic Clinical-Immunological Profiles of Human Infection by Leishmania (L.) chagasi in Amazonian Brazil
title_sort gene signatures of symptomatic and asymptomatic clinical-immunological profiles of human infection by leishmania (l.) chagasi in amazonian brazil
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10058599/
https://www.ncbi.nlm.nih.gov/pubmed/36985226
http://dx.doi.org/10.3390/microorganisms11030653
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