Toxoplasma gondii infection and peripheral-blood gene expression profiling of older people reveals dysregulation of cytokines and identifies hub genes as potential therapeutic targets
Infections of humans with the protozoan parasite Toxoplasma gondii (T. gondii) can lead to the disease's development, even in an asymptomatic status. However, the mechanisms that result in these clinical outcomes after infection are poorly understood. This study aimed to explore the molecular p...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-09-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844022018643 |
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| author | Carlos A. Naranjo-Galvis Kelly Y. Cardona-Londoño Mary Orrego-Cardozo Xabier Elcoroaristizabal-Martín |
| author_facet | Carlos A. Naranjo-Galvis Kelly Y. Cardona-Londoño Mary Orrego-Cardozo Xabier Elcoroaristizabal-Martín |
| author_sort | Carlos A. Naranjo-Galvis |
| collection | DOAJ |
| description | Infections of humans with the protozoan parasite Toxoplasma gondii (T. gondii) can lead to the disease's development, even in an asymptomatic status. However, the mechanisms that result in these clinical outcomes after infection are poorly understood. This study aimed to explore the molecular pathogenesis of toxoplasmosis-related inflammation through next-generation sequencing, to assess RNA expression profiles in peripheral blood from 5 female patients with chronic toxoplasmosis and 5 healthy female controls. All plasma samples were analyzed for anti-Toxoplasma IgG and IgM antibody titers by using electrochemiluminescence. Detection of acute and chronic toxoplasmosis was carried out using the ELISA IgG avidity. We evaluated the levels of INF-γ, IL-2, IL-12, TNF-α, IL-10, and IL-1β in culture supernatants of Peripheral Blood Mononuclear Cells infected with Toxoplasma lysate antigen (TLA) prepared with tachyzoites of strain T. gondii RH. Differential expression analysis was performed using DESeq2, pathway and enrichment analysis of DEGs was done on WEB-based Gene SeT AnaLysis Toolkit (WebGestalt) and Protein-protein interaction was carried out using NetworkAnalyst with STRING. In older people with chronic asymptomatic infection, a significant difference in the levels of inflammatory cytokines INF-γ and IL-2 was observed compared to seronegative individuals. Our results revealed differences in the regulation of critical biological processes involved in host responses to chronic T. gondii infection. Gene ontology analysis revealed several biologically relevant inflammatory and immune-related pathways. |
| first_indexed | 2024-04-12T03:46:22Z |
| format | Article |
| id | doaj.art-610df122964547ae822906a98205cf6f |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-12T03:46:22Z |
| publishDate | 2022-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-610df122964547ae822906a98205cf6f2022-12-22T03:49:08ZengElsevierHeliyon2405-84402022-09-0189e10576Toxoplasma gondii infection and peripheral-blood gene expression profiling of older people reveals dysregulation of cytokines and identifies hub genes as potential therapeutic targetsCarlos A. Naranjo-Galvis0Kelly Y. Cardona-Londoño1Mary Orrego-Cardozo2Xabier Elcoroaristizabal-Martín3Facultad de Salud, Universidad Autónoma de Manizales, Antigua Estación Del Ferrocarril, Manizales, Caldas, Colombia; Corresponding author.Facultad de Salud, Universidad Autónoma de Manizales, Antigua Estación Del Ferrocarril, Manizales, Caldas, ColombiaFacultad de Salud, Universidad Autónoma de Manizales, Antigua Estación Del Ferrocarril, Manizales, Caldas, ColombiaGenetracer Biotech, Santander, SpainInfections of humans with the protozoan parasite Toxoplasma gondii (T. gondii) can lead to the disease's development, even in an asymptomatic status. However, the mechanisms that result in these clinical outcomes after infection are poorly understood. This study aimed to explore the molecular pathogenesis of toxoplasmosis-related inflammation through next-generation sequencing, to assess RNA expression profiles in peripheral blood from 5 female patients with chronic toxoplasmosis and 5 healthy female controls. All plasma samples were analyzed for anti-Toxoplasma IgG and IgM antibody titers by using electrochemiluminescence. Detection of acute and chronic toxoplasmosis was carried out using the ELISA IgG avidity. We evaluated the levels of INF-γ, IL-2, IL-12, TNF-α, IL-10, and IL-1β in culture supernatants of Peripheral Blood Mononuclear Cells infected with Toxoplasma lysate antigen (TLA) prepared with tachyzoites of strain T. gondii RH. Differential expression analysis was performed using DESeq2, pathway and enrichment analysis of DEGs was done on WEB-based Gene SeT AnaLysis Toolkit (WebGestalt) and Protein-protein interaction was carried out using NetworkAnalyst with STRING. In older people with chronic asymptomatic infection, a significant difference in the levels of inflammatory cytokines INF-γ and IL-2 was observed compared to seronegative individuals. Our results revealed differences in the regulation of critical biological processes involved in host responses to chronic T. gondii infection. Gene ontology analysis revealed several biologically relevant inflammatory and immune-related pathways.http://www.sciencedirect.com/science/article/pii/S2405844022018643Toxoplasma gondiiHost-pathogen interactionOlder peopleInflammationCytokinesRNA Ion AmpliSeq |
| spellingShingle | Carlos A. Naranjo-Galvis Kelly Y. Cardona-Londoño Mary Orrego-Cardozo Xabier Elcoroaristizabal-Martín Toxoplasma gondii infection and peripheral-blood gene expression profiling of older people reveals dysregulation of cytokines and identifies hub genes as potential therapeutic targets Heliyon Toxoplasma gondii Host-pathogen interaction Older people Inflammation Cytokines RNA Ion AmpliSeq |
| title | Toxoplasma gondii infection and peripheral-blood gene expression profiling of older people reveals dysregulation of cytokines and identifies hub genes as potential therapeutic targets |
| title_full | Toxoplasma gondii infection and peripheral-blood gene expression profiling of older people reveals dysregulation of cytokines and identifies hub genes as potential therapeutic targets |
| title_fullStr | Toxoplasma gondii infection and peripheral-blood gene expression profiling of older people reveals dysregulation of cytokines and identifies hub genes as potential therapeutic targets |
| title_full_unstemmed | Toxoplasma gondii infection and peripheral-blood gene expression profiling of older people reveals dysregulation of cytokines and identifies hub genes as potential therapeutic targets |
| title_short | Toxoplasma gondii infection and peripheral-blood gene expression profiling of older people reveals dysregulation of cytokines and identifies hub genes as potential therapeutic targets |
| title_sort | toxoplasma gondii infection and peripheral blood gene expression profiling of older people reveals dysregulation of cytokines and identifies hub genes as potential therapeutic targets |
| topic | Toxoplasma gondii Host-pathogen interaction Older people Inflammation Cytokines RNA Ion AmpliSeq |
| url | http://www.sciencedirect.com/science/article/pii/S2405844022018643 |
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