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Article

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

by
Vania Lucia R. da Matta
1,
André N. Gonçalves
1,
Cláudia Maria C. Gomes
1,
Islam H. Chouman
1,
Frederico M. Ferreira
1,
Marliane B. Campos
2,
Luciana V. Lima
2,
Thiago Vasconcelos dos Santos
2,
Patrícia Karla Ramos
2,
Rodrigo R. Furtado
2,
Marcia D. Laurenti
1,
Carlos Eduardo P. Corbett
1,
Helder I. Nakaya
3,4,*,† and
Fernando T. Silveira
2,5,*,†
1
Laboratorio de Patologia de Molestias Infecciosas (LIM-50), Departamento de Patologia, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 01246 903, Brazil
2
Parasitology Department, Evandro Chagas Institute, Health Surveillance Secretary, Ministry of Health, Ananindeua 67030-000, Brazil
3
Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciencias Farmaceuticas, Universidade de Sao Paulo, Sao Paulo 05508-220, Brazil
4
Hospital Israelita Albert Einstein, Sao Paulo 05652-900, Brazil
5
Tropical Medicine Nucleus, Pará Federal University, Belém 67030-000, Brazil
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Microorganisms 2023, 11(3), 653; https://doi.org/10.3390/microorganisms11030653
Submission received: 1 February 2023 / Revised: 18 February 2023 / Accepted: 28 February 2023 / Published: 3 March 2023
(This article belongs to the Special Issue Parasitic Infection and Host Immunity, 2nd Edition)

Abstract

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.
Keywords: Leishmania (L.) chagasi; human infection; transcriptomic analysis; symptomatic; asymptomatic; clinical-immunological profiles Leishmania (L.) chagasi; human infection; transcriptomic analysis; symptomatic; asymptomatic; clinical-immunological profiles

Share and Cite

MDPI and ACS Style

da Matta, V.L.R.; Gonçalves, A.N.; Gomes, C.M.C.; Chouman, I.H.; Ferreira, F.M.; Campos, M.B.; Lima, L.V.; Vasconcelos dos Santos, T.; Ramos, P.K.; Furtado, R.R.; et al. Gene Signatures of Symptomatic and Asymptomatic Clinical-Immunological Profiles of Human Infection by Leishmania (L.) chagasi in Amazonian Brazil. Microorganisms 2023, 11, 653. https://doi.org/10.3390/microorganisms11030653

AMA Style

da Matta VLR, Gonçalves AN, Gomes CMC, Chouman IH, Ferreira FM, Campos MB, Lima LV, Vasconcelos dos Santos T, Ramos PK, Furtado RR, et al. Gene Signatures of Symptomatic and Asymptomatic Clinical-Immunological Profiles of Human Infection by Leishmania (L.) chagasi in Amazonian Brazil. Microorganisms. 2023; 11(3):653. https://doi.org/10.3390/microorganisms11030653

Chicago/Turabian Style

da Matta, Vania Lucia R., André N. Gonçalves, Cláudia Maria C. Gomes, Islam H. Chouman, Frederico M. Ferreira, Marliane B. Campos, Luciana V. Lima, Thiago Vasconcelos dos Santos, Patrícia Karla Ramos, Rodrigo R. Furtado, and et al. 2023. "Gene Signatures of Symptomatic and Asymptomatic Clinical-Immunological Profiles of Human Infection by Leishmania (L.) chagasi in Amazonian Brazil" Microorganisms 11, no. 3: 653. https://doi.org/10.3390/microorganisms11030653

APA Style

da Matta, V. L. R., Gonçalves, A. N., Gomes, C. M. C., Chouman, I. H., Ferreira, F. M., Campos, M. B., Lima, L. V., Vasconcelos dos Santos, T., Ramos, P. K., Furtado, R. R., Laurenti, M. D., Corbett, C. E. P., Nakaya, H. I., & Silveira, F. T. (2023). Gene Signatures of Symptomatic and Asymptomatic Clinical-Immunological Profiles of Human Infection by Leishmania (L.) chagasi in Amazonian Brazil. Microorganisms, 11(3), 653. https://doi.org/10.3390/microorganisms11030653

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