Transcriptional profiling of macrophages reveals distinct parasite stage-driven signatures during early infection by Leishmania donovani
Abstract Macrophages undergo swift changes in mRNA abundance upon pathogen invasion. Herein we describe early remodelling of the macrophage transcriptome during infection by amastigotes or promastigotes of Leishmania donovani. Approximately 10–16% of host mRNAs were differentially modulated in L. do...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-10317-6 |
| _version_ | 1811302975732187136 |
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| author | Visnu Chaparro Tyson E. Graber Tommy Alain Maritza Jaramillo |
| author_facet | Visnu Chaparro Tyson E. Graber Tommy Alain Maritza Jaramillo |
| author_sort | Visnu Chaparro |
| collection | DOAJ |
| description | Abstract Macrophages undergo swift changes in mRNA abundance upon pathogen invasion. Herein we describe early remodelling of the macrophage transcriptome during infection by amastigotes or promastigotes of Leishmania donovani. Approximately 10–16% of host mRNAs were differentially modulated in L. donovani-infected macrophages when compared to uninfected controls. This response was partially stage-specific as a third of changes in mRNA abundance were either exclusively driven by one of the parasite forms or significantly different between them. Gene ontology analyses identified categories associated with immune functions (e.g. antigen presentation and leukocyte activation) among significantly downregulated mRNAs during amastigote infection while cytoprotective-related categories (e.g. DNA repair and apoptosis inhibition) were enriched in upregulated transcripts. Interestingly a combination of upregulated (e.g. cellular response to IFNβ) and repressed (e.g. leukocyte activation, chemotaxis) immune-related transcripts were overrepresented in the promastigote-infected dataset. In addition, Ingenuity Pathway Analysis (IPA) associated specific mRNA subsets with a number of upstream transcriptional regulators predicted to be modulated in macrophages infected with L. donovani amastigotes (e.g. STAT1 inhibition) or promastigotes (e.g. NRF2, IRF3, and IRF7 activation). Overall, our results indicate that early parasite stage-driven transcriptional remodelling in macrophages contributes to orchestrate both protective and deleterious host cell responses during L. donovani infection. |
| first_indexed | 2024-04-13T07:38:57Z |
| format | Article |
| id | doaj.art-2de07c19a05349b580e296cb4d8e7cc8 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-13T07:38:57Z |
| publishDate | 2022-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-2de07c19a05349b580e296cb4d8e7cc82022-12-22T02:55:57ZengNature PortfolioScientific Reports2045-23222022-04-0112111310.1038/s41598-022-10317-6Transcriptional profiling of macrophages reveals distinct parasite stage-driven signatures during early infection by Leishmania donovaniVisnu Chaparro0Tyson E. Graber1Tommy Alain2Maritza Jaramillo3Institut National de la Recherche Scientifique (INRS) – Centre Armand-Frappier Santé Biotechnologie (AFSB)Children’s Hospital of Eastern Ontario Research InstituteChildren’s Hospital of Eastern Ontario Research InstituteInstitut National de la Recherche Scientifique (INRS) – Centre Armand-Frappier Santé Biotechnologie (AFSB)Abstract Macrophages undergo swift changes in mRNA abundance upon pathogen invasion. Herein we describe early remodelling of the macrophage transcriptome during infection by amastigotes or promastigotes of Leishmania donovani. Approximately 10–16% of host mRNAs were differentially modulated in L. donovani-infected macrophages when compared to uninfected controls. This response was partially stage-specific as a third of changes in mRNA abundance were either exclusively driven by one of the parasite forms or significantly different between them. Gene ontology analyses identified categories associated with immune functions (e.g. antigen presentation and leukocyte activation) among significantly downregulated mRNAs during amastigote infection while cytoprotective-related categories (e.g. DNA repair and apoptosis inhibition) were enriched in upregulated transcripts. Interestingly a combination of upregulated (e.g. cellular response to IFNβ) and repressed (e.g. leukocyte activation, chemotaxis) immune-related transcripts were overrepresented in the promastigote-infected dataset. In addition, Ingenuity Pathway Analysis (IPA) associated specific mRNA subsets with a number of upstream transcriptional regulators predicted to be modulated in macrophages infected with L. donovani amastigotes (e.g. STAT1 inhibition) or promastigotes (e.g. NRF2, IRF3, and IRF7 activation). Overall, our results indicate that early parasite stage-driven transcriptional remodelling in macrophages contributes to orchestrate both protective and deleterious host cell responses during L. donovani infection.https://doi.org/10.1038/s41598-022-10317-6 |
| spellingShingle | Visnu Chaparro Tyson E. Graber Tommy Alain Maritza Jaramillo Transcriptional profiling of macrophages reveals distinct parasite stage-driven signatures during early infection by Leishmania donovani Scientific Reports |
| title | Transcriptional profiling of macrophages reveals distinct parasite stage-driven signatures during early infection by Leishmania donovani |
| title_full | Transcriptional profiling of macrophages reveals distinct parasite stage-driven signatures during early infection by Leishmania donovani |
| title_fullStr | Transcriptional profiling of macrophages reveals distinct parasite stage-driven signatures during early infection by Leishmania donovani |
| title_full_unstemmed | Transcriptional profiling of macrophages reveals distinct parasite stage-driven signatures during early infection by Leishmania donovani |
| title_short | Transcriptional profiling of macrophages reveals distinct parasite stage-driven signatures during early infection by Leishmania donovani |
| title_sort | transcriptional profiling of macrophages reveals distinct parasite stage driven signatures during early infection by leishmania donovani |
| url | https://doi.org/10.1038/s41598-022-10317-6 |
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