Gene Signatures of Symptomatic and Asymptomatic Clinical-Immunological Profiles of Human Infection by <i>Leishmania</i> (<i>L.</i>) <i>chagasi</i> in Amazonian Brazil
Individuals infected with <i>Leishmania</i> (<i>L.</i>) <i>chagasi</i> 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 resi...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-03-01
|
| Series: | Microorganisms |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-2607/11/3/653 |
| _version_ | 1797609983254200320 |
|---|---|
| author | Vania Lucia R. da Matta 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 Marcia D. Laurenti Carlos Eduardo P. Corbett Helder I. Nakaya Fernando T. Silveira |
| author_facet | Vania Lucia R. da Matta 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 Marcia D. Laurenti Carlos Eduardo P. Corbett Helder I. Nakaya Fernando T. Silveira |
| author_sort | Vania Lucia R. da Matta |
| collection | DOAJ |
| description | Individuals infected with <i>Leishmania</i> (<i>L.</i>) <i>chagasi</i> 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 <i>L.</i> (<i>L.</i>) <i>chagasi</i>-infection in the Brazilian Amazon. |
| first_indexed | 2024-03-11T06:09:04Z |
| format | Article |
| id | doaj.art-2a11ef152a184bffbda8ec68284c988d |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-11T06:09:04Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-2a11ef152a184bffbda8ec68284c988d2023-11-17T12:45:14ZengMDPI AGMicroorganisms2076-26072023-03-0111365310.3390/microorganisms11030653Gene Signatures of Symptomatic and Asymptomatic Clinical-Immunological Profiles of Human Infection by <i>Leishmania</i> (<i>L.</i>) <i>chagasi</i> in Amazonian BrazilVania Lucia R. da Matta0André N. Gonçalves1Cláudia Maria C. Gomes2Islam H. Chouman3Frederico M. Ferreira4Marliane B. Campos5Luciana V. Lima6Thiago Vasconcelos dos Santos7Patrícia Karla Ramos8Rodrigo R. Furtado9Marcia D. Laurenti10Carlos Eduardo P. Corbett11Helder I. Nakaya12Fernando T. Silveira13Laboratorio de Patologia de Molestias Infecciosas (LIM-50), Departamento de Patologia, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 01246 903, BrazilLaboratorio de Patologia de Molestias Infecciosas (LIM-50), Departamento de Patologia, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 01246 903, BrazilLaboratorio de Patologia de Molestias Infecciosas (LIM-50), Departamento de Patologia, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 01246 903, BrazilLaboratorio de Patologia de Molestias Infecciosas (LIM-50), Departamento de Patologia, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 01246 903, BrazilLaboratorio de Patologia de Molestias Infecciosas (LIM-50), Departamento de Patologia, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 01246 903, BrazilParasitology Department, Evandro Chagas Institute, Health Surveillance Secretary, Ministry of Health, Ananindeua 67030-000, BrazilParasitology Department, Evandro Chagas Institute, Health Surveillance Secretary, Ministry of Health, Ananindeua 67030-000, BrazilParasitology Department, Evandro Chagas Institute, Health Surveillance Secretary, Ministry of Health, Ananindeua 67030-000, BrazilParasitology Department, Evandro Chagas Institute, Health Surveillance Secretary, Ministry of Health, Ananindeua 67030-000, BrazilParasitology Department, Evandro Chagas Institute, Health Surveillance Secretary, Ministry of Health, Ananindeua 67030-000, BrazilLaboratorio de Patologia de Molestias Infecciosas (LIM-50), Departamento de Patologia, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 01246 903, BrazilLaboratorio de Patologia de Molestias Infecciosas (LIM-50), Departamento de Patologia, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 01246 903, BrazilDepartamento de Análises Clínicas e Toxicológicas, Faculdade de Ciencias Farmaceuticas, Universidade de Sao Paulo, Sao Paulo 05508-220, BrazilParasitology Department, Evandro Chagas Institute, Health Surveillance Secretary, Ministry of Health, Ananindeua 67030-000, BrazilIndividuals infected with <i>Leishmania</i> (<i>L.</i>) <i>chagasi</i> 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 <i>L.</i> (<i>L.</i>) <i>chagasi</i>-infection in the Brazilian Amazon.https://www.mdpi.com/2076-2607/11/3/653<i>Leishmania</i> (<i>L.</i>) <i>chagasi</i>human infectiontranscriptomic analysissymptomaticasymptomaticclinical-immunological profiles |
| spellingShingle | Vania Lucia R. da Matta 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 Marcia D. Laurenti Carlos Eduardo P. Corbett Helder I. Nakaya Fernando T. Silveira Gene Signatures of Symptomatic and Asymptomatic Clinical-Immunological Profiles of Human Infection by <i>Leishmania</i> (<i>L.</i>) <i>chagasi</i> in Amazonian Brazil Microorganisms <i>Leishmania</i> (<i>L.</i>) <i>chagasi</i> human infection transcriptomic analysis symptomatic asymptomatic clinical-immunological profiles |
| title | Gene Signatures of Symptomatic and Asymptomatic Clinical-Immunological Profiles of Human Infection by <i>Leishmania</i> (<i>L.</i>) <i>chagasi</i> in Amazonian Brazil |
| title_full | Gene Signatures of Symptomatic and Asymptomatic Clinical-Immunological Profiles of Human Infection by <i>Leishmania</i> (<i>L.</i>) <i>chagasi</i> in Amazonian Brazil |
| title_fullStr | Gene Signatures of Symptomatic and Asymptomatic Clinical-Immunological Profiles of Human Infection by <i>Leishmania</i> (<i>L.</i>) <i>chagasi</i> in Amazonian Brazil |
| title_full_unstemmed | Gene Signatures of Symptomatic and Asymptomatic Clinical-Immunological Profiles of Human Infection by <i>Leishmania</i> (<i>L.</i>) <i>chagasi</i> in Amazonian Brazil |
| title_short | Gene Signatures of Symptomatic and Asymptomatic Clinical-Immunological Profiles of Human Infection by <i>Leishmania</i> (<i>L.</i>) <i>chagasi</i> in Amazonian Brazil |
| title_sort | gene signatures of symptomatic and asymptomatic clinical immunological profiles of human infection by i leishmania i i l i i chagasi i in amazonian brazil |
| topic | <i>Leishmania</i> (<i>L.</i>) <i>chagasi</i> human infection transcriptomic analysis symptomatic asymptomatic clinical-immunological profiles |
| url | https://www.mdpi.com/2076-2607/11/3/653 |
| work_keys_str_mv | AT vanialuciardamatta genesignaturesofsymptomaticandasymptomaticclinicalimmunologicalprofilesofhumaninfectionbyileishmaniaiiliichagasiiinamazonianbrazil AT andrengoncalves genesignaturesofsymptomaticandasymptomaticclinicalimmunologicalprofilesofhumaninfectionbyileishmaniaiiliichagasiiinamazonianbrazil AT claudiamariacgomes genesignaturesofsymptomaticandasymptomaticclinicalimmunologicalprofilesofhumaninfectionbyileishmaniaiiliichagasiiinamazonianbrazil AT islamhchouman genesignaturesofsymptomaticandasymptomaticclinicalimmunologicalprofilesofhumaninfectionbyileishmaniaiiliichagasiiinamazonianbrazil AT fredericomferreira genesignaturesofsymptomaticandasymptomaticclinicalimmunologicalprofilesofhumaninfectionbyileishmaniaiiliichagasiiinamazonianbrazil AT marlianebcampos genesignaturesofsymptomaticandasymptomaticclinicalimmunologicalprofilesofhumaninfectionbyileishmaniaiiliichagasiiinamazonianbrazil AT lucianavlima genesignaturesofsymptomaticandasymptomaticclinicalimmunologicalprofilesofhumaninfectionbyileishmaniaiiliichagasiiinamazonianbrazil AT thiagovasconcelosdossantos genesignaturesofsymptomaticandasymptomaticclinicalimmunologicalprofilesofhumaninfectionbyileishmaniaiiliichagasiiinamazonianbrazil AT patriciakarlaramos genesignaturesofsymptomaticandasymptomaticclinicalimmunologicalprofilesofhumaninfectionbyileishmaniaiiliichagasiiinamazonianbrazil AT rodrigorfurtado genesignaturesofsymptomaticandasymptomaticclinicalimmunologicalprofilesofhumaninfectionbyileishmaniaiiliichagasiiinamazonianbrazil AT marciadlaurenti genesignaturesofsymptomaticandasymptomaticclinicalimmunologicalprofilesofhumaninfectionbyileishmaniaiiliichagasiiinamazonianbrazil AT carloseduardopcorbett genesignaturesofsymptomaticandasymptomaticclinicalimmunologicalprofilesofhumaninfectionbyileishmaniaiiliichagasiiinamazonianbrazil AT helderinakaya genesignaturesofsymptomaticandasymptomaticclinicalimmunologicalprofilesofhumaninfectionbyileishmaniaiiliichagasiiinamazonianbrazil AT fernandotsilveira genesignaturesofsymptomaticandasymptomaticclinicalimmunologicalprofilesofhumaninfectionbyileishmaniaiiliichagasiiinamazonianbrazil |