Expression Profile of Genes Related to the Th17 Pathway in Macrophages Infected by Leishmania major and Leishmania amazonensis: The Use of Gene Regulatory Networks in Modeling This Pathway
Leishmania amazonensis and Leishmania major are the causative agents of cutaneous and mucocutaneous diseases. The infections‘ outcome depends on host–parasite interactions and Th1/Th2 response, and in cutaneous form, regulation of Th17 cytokines has been reported to maintain inflammation in lesions....
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-06-01
|
| Series: | Frontiers in Cellular and Infection Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2022.826523/full |
| _version_ | 1828793949454598144 |
|---|---|
| author | Leilane Oliveira Gonçalves Leilane Oliveira Gonçalves Andrés F. Vallejo Pulido Fernando Augusto Siqueira Mathias Alexandre Estevão Silvério Enes Alexandre Estevão Silvério Enes Maria Gabriela Reis Carvalho Daniela de Melo Resende Marta E. Polak Jeronimo C. Ruiz |
| author_facet | Leilane Oliveira Gonçalves Leilane Oliveira Gonçalves Andrés F. Vallejo Pulido Fernando Augusto Siqueira Mathias Alexandre Estevão Silvério Enes Alexandre Estevão Silvério Enes Maria Gabriela Reis Carvalho Daniela de Melo Resende Marta E. Polak Jeronimo C. Ruiz |
| author_sort | Leilane Oliveira Gonçalves |
| collection | DOAJ |
| description | Leishmania amazonensis and Leishmania major are the causative agents of cutaneous and mucocutaneous diseases. The infections‘ outcome depends on host–parasite interactions and Th1/Th2 response, and in cutaneous form, regulation of Th17 cytokines has been reported to maintain inflammation in lesions. Despite that, the Th17 regulatory scenario remains unclear. With the aim to gain a better understanding of the transcription factors (TFs) and genes involved in Th17 induction, in this study, the role of inducing factors of the Th17 pathway in Leishmania–macrophage infection was addressed through computational modeling of gene regulatory networks (GRNs). The Th17 GRN modeling integrated experimentally validated data available in the literature and gene expression data from a time-series RNA-seq experiment (4, 24, 48, and 72 h post-infection). The generated model comprises a total of 10 TFs, 22 coding genes, and 16 cytokines related to the Th17 immune modulation. Addressing the Th17 induction in infected and uninfected macrophages, an increase of 2- to 3-fold in 4–24 h was observed in the former. However, there was a decrease in basal levels at 48–72 h for both groups. In order to evaluate the possible outcomes triggered by GRN component modulation in the Th17 pathway. The generated GRN models promoted an integrative and dynamic view of Leishmania–macrophage interaction over time that extends beyond the analysis of single-gene expression. |
| first_indexed | 2024-12-12T03:36:49Z |
| format | Article |
| id | doaj.art-63f8b76b136e447eb52c9620b10e1355 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-12T03:36:49Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-63f8b76b136e447eb52c9620b10e13552022-12-22T00:39:47ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882022-06-011210.3389/fcimb.2022.826523826523Expression Profile of Genes Related to the Th17 Pathway in Macrophages Infected by Leishmania major and Leishmania amazonensis: The Use of Gene Regulatory Networks in Modeling This PathwayLeilane Oliveira Gonçalves0Leilane Oliveira Gonçalves1Andrés F. Vallejo Pulido2Fernando Augusto Siqueira Mathias3Alexandre Estevão Silvério Enes4Alexandre Estevão Silvério Enes5Maria Gabriela Reis Carvalho6Daniela de Melo Resende7Marta E. Polak8Jeronimo C. Ruiz9Programa de Pós-graduação em Biologia Computacional e Sistemas, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, BrazilGrupo Informática de Biossistemas, Instituto René Rachou, Fiocruz Minas, Belo Horizonte, BrazilSystems Immunology Group, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United KingdomGrupo Informática de Biossistemas, Instituto René Rachou, Fiocruz Minas, Belo Horizonte, BrazilPrograma de Pós-graduação em Biologia Computacional e Sistemas, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, BrazilGrupo Informática de Biossistemas, Instituto René Rachou, Fiocruz Minas, Belo Horizonte, BrazilGrupo Informática de Biossistemas, Instituto René Rachou, Fiocruz Minas, Belo Horizonte, BrazilGrupo Genômica Funcional de Parasitos, Instituto René Rachou, Fiocruz Minas, Belo Horizonte, BrazilSystems Immunology Group, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United KingdomGrupo Informática de Biossistemas, Instituto René Rachou, Fiocruz Minas, Belo Horizonte, BrazilLeishmania amazonensis and Leishmania major are the causative agents of cutaneous and mucocutaneous diseases. The infections‘ outcome depends on host–parasite interactions and Th1/Th2 response, and in cutaneous form, regulation of Th17 cytokines has been reported to maintain inflammation in lesions. Despite that, the Th17 regulatory scenario remains unclear. With the aim to gain a better understanding of the transcription factors (TFs) and genes involved in Th17 induction, in this study, the role of inducing factors of the Th17 pathway in Leishmania–macrophage infection was addressed through computational modeling of gene regulatory networks (GRNs). The Th17 GRN modeling integrated experimentally validated data available in the literature and gene expression data from a time-series RNA-seq experiment (4, 24, 48, and 72 h post-infection). The generated model comprises a total of 10 TFs, 22 coding genes, and 16 cytokines related to the Th17 immune modulation. Addressing the Th17 induction in infected and uninfected macrophages, an increase of 2- to 3-fold in 4–24 h was observed in the former. However, there was a decrease in basal levels at 48–72 h for both groups. In order to evaluate the possible outcomes triggered by GRN component modulation in the Th17 pathway. The generated GRN models promoted an integrative and dynamic view of Leishmania–macrophage interaction over time that extends beyond the analysis of single-gene expression.https://www.frontiersin.org/articles/10.3389/fcimb.2022.826523/fullLeishmania–macrophage interactiongene regulatory network (GRN)expression profilingTh17immune modulation |
| spellingShingle | Leilane Oliveira Gonçalves Leilane Oliveira Gonçalves Andrés F. Vallejo Pulido Fernando Augusto Siqueira Mathias Alexandre Estevão Silvério Enes Alexandre Estevão Silvério Enes Maria Gabriela Reis Carvalho Daniela de Melo Resende Marta E. Polak Jeronimo C. Ruiz Expression Profile of Genes Related to the Th17 Pathway in Macrophages Infected by Leishmania major and Leishmania amazonensis: The Use of Gene Regulatory Networks in Modeling This Pathway Frontiers in Cellular and Infection Microbiology Leishmania–macrophage interaction gene regulatory network (GRN) expression profiling Th17 immune modulation |
| title | Expression Profile of Genes Related to the Th17 Pathway in Macrophages Infected by Leishmania major and Leishmania amazonensis: The Use of Gene Regulatory Networks in Modeling This Pathway |
| title_full | Expression Profile of Genes Related to the Th17 Pathway in Macrophages Infected by Leishmania major and Leishmania amazonensis: The Use of Gene Regulatory Networks in Modeling This Pathway |
| title_fullStr | Expression Profile of Genes Related to the Th17 Pathway in Macrophages Infected by Leishmania major and Leishmania amazonensis: The Use of Gene Regulatory Networks in Modeling This Pathway |
| title_full_unstemmed | Expression Profile of Genes Related to the Th17 Pathway in Macrophages Infected by Leishmania major and Leishmania amazonensis: The Use of Gene Regulatory Networks in Modeling This Pathway |
| title_short | Expression Profile of Genes Related to the Th17 Pathway in Macrophages Infected by Leishmania major and Leishmania amazonensis: The Use of Gene Regulatory Networks in Modeling This Pathway |
| title_sort | expression profile of genes related to the th17 pathway in macrophages infected by leishmania major and leishmania amazonensis the use of gene regulatory networks in modeling this pathway |
| topic | Leishmania–macrophage interaction gene regulatory network (GRN) expression profiling Th17 immune modulation |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2022.826523/full |
| work_keys_str_mv | AT leilaneoliveiragoncalves expressionprofileofgenesrelatedtotheth17pathwayinmacrophagesinfectedbyleishmaniamajorandleishmaniaamazonensistheuseofgeneregulatorynetworksinmodelingthispathway AT leilaneoliveiragoncalves expressionprofileofgenesrelatedtotheth17pathwayinmacrophagesinfectedbyleishmaniamajorandleishmaniaamazonensistheuseofgeneregulatorynetworksinmodelingthispathway AT andresfvallejopulido expressionprofileofgenesrelatedtotheth17pathwayinmacrophagesinfectedbyleishmaniamajorandleishmaniaamazonensistheuseofgeneregulatorynetworksinmodelingthispathway AT fernandoaugustosiqueiramathias expressionprofileofgenesrelatedtotheth17pathwayinmacrophagesinfectedbyleishmaniamajorandleishmaniaamazonensistheuseofgeneregulatorynetworksinmodelingthispathway AT alexandreestevaosilverioenes expressionprofileofgenesrelatedtotheth17pathwayinmacrophagesinfectedbyleishmaniamajorandleishmaniaamazonensistheuseofgeneregulatorynetworksinmodelingthispathway AT alexandreestevaosilverioenes expressionprofileofgenesrelatedtotheth17pathwayinmacrophagesinfectedbyleishmaniamajorandleishmaniaamazonensistheuseofgeneregulatorynetworksinmodelingthispathway AT mariagabrielareiscarvalho expressionprofileofgenesrelatedtotheth17pathwayinmacrophagesinfectedbyleishmaniamajorandleishmaniaamazonensistheuseofgeneregulatorynetworksinmodelingthispathway AT danielademeloresende expressionprofileofgenesrelatedtotheth17pathwayinmacrophagesinfectedbyleishmaniamajorandleishmaniaamazonensistheuseofgeneregulatorynetworksinmodelingthispathway AT martaepolak expressionprofileofgenesrelatedtotheth17pathwayinmacrophagesinfectedbyleishmaniamajorandleishmaniaamazonensistheuseofgeneregulatorynetworksinmodelingthispathway AT jeronimocruiz expressionprofileofgenesrelatedtotheth17pathwayinmacrophagesinfectedbyleishmaniamajorandleishmaniaamazonensistheuseofgeneregulatorynetworksinmodelingthispathway |