In vivo transcriptional analysis of mice infected with Leishmania major unveils cellular heterogeneity and altered transcriptomic profiling at single-cell resolution.
Leishmania parasites cause cutaneous leishmaniasis (CL), a disease characterized by disfiguring, ulcerative skin lesions. Both parasite and host gene expression following infection with various Leishmania species has been investigated in vitro, but global transcriptional analysis following L. major...
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ftdoajarticles:oai:doaj.org/article:d26927c033344c0ea181b3edfa3c7df2 2023-05-15T15:10:48+02:00 In vivo transcriptional analysis of mice infected with Leishmania major unveils cellular heterogeneity and altered transcriptomic profiling at single-cell resolution. Gopinath Venugopal Jordan T Bird Charity L Washam Hayden Roys Anne Bowlin Stephanie D Byrum Tiffany Weinkopff 2022-07-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0010518 https://doaj.org/article/d26927c033344c0ea181b3edfa3c7df2 EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0010518 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0010518 https://doaj.org/article/d26927c033344c0ea181b3edfa3c7df2 PLoS Neglected Tropical Diseases, Vol 16, Iss 7, p e0010518 (2022) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2022 ftdoajarticles https://doi.org/10.1371/journal.pntd.0010518 2022-12-31T01:05:24Z Leishmania parasites cause cutaneous leishmaniasis (CL), a disease characterized by disfiguring, ulcerative skin lesions. Both parasite and host gene expression following infection with various Leishmania species has been investigated in vitro, but global transcriptional analysis following L. major infection in vivo is lacking. Thus, we conducted a comprehensive transcriptomic profiling study combining bulk RNA sequencing (RNA-Seq) and single-cell RNA sequencing (scRNA-Seq) to identify global changes in gene expression in vivo following L. major infection. Bulk RNA-Seq analysis revealed that host immune response pathways like the antigen processing and presentation pathway were significantly enriched amongst differentially expressed genes (DEGs) upon infection, while ribosomal pathways were significantly downregulated in infected mice compared to naive controls. scRNA-Seq analyses revealed cellular heterogeneity including distinct resident and recruited cell types in the skin following murine L. major infection. Within the individual immune cell types, several DEGs indicative of many interferon induced GTPases and antigen presentation molecules were significantly enhanced in the infected ears including macrophages, resident macrophages, and inflammatory monocytes. Ingenuity Pathway Analysis of scRNA-Seq data indicated the antigen presentation pathway was increased with infection, while EIF2 signaling is the top downregulated pathway followed by eIF4/p70S6k and mTOR signaling in multiple cell types including macrophages, blood and lymphatic endothelial cells. Altogether, this transcriptomic profile highlights known recruitment of myeloid cells to lesions and recognizes a potential role for EIF2 signaling in murine L. major infection in vivo. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 16 7 e0010518 |
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Directory of Open Access Journals: DOAJ Articles |
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English |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Gopinath Venugopal Jordan T Bird Charity L Washam Hayden Roys Anne Bowlin Stephanie D Byrum Tiffany Weinkopff In vivo transcriptional analysis of mice infected with Leishmania major unveils cellular heterogeneity and altered transcriptomic profiling at single-cell resolution. |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Leishmania parasites cause cutaneous leishmaniasis (CL), a disease characterized by disfiguring, ulcerative skin lesions. Both parasite and host gene expression following infection with various Leishmania species has been investigated in vitro, but global transcriptional analysis following L. major infection in vivo is lacking. Thus, we conducted a comprehensive transcriptomic profiling study combining bulk RNA sequencing (RNA-Seq) and single-cell RNA sequencing (scRNA-Seq) to identify global changes in gene expression in vivo following L. major infection. Bulk RNA-Seq analysis revealed that host immune response pathways like the antigen processing and presentation pathway were significantly enriched amongst differentially expressed genes (DEGs) upon infection, while ribosomal pathways were significantly downregulated in infected mice compared to naive controls. scRNA-Seq analyses revealed cellular heterogeneity including distinct resident and recruited cell types in the skin following murine L. major infection. Within the individual immune cell types, several DEGs indicative of many interferon induced GTPases and antigen presentation molecules were significantly enhanced in the infected ears including macrophages, resident macrophages, and inflammatory monocytes. Ingenuity Pathway Analysis of scRNA-Seq data indicated the antigen presentation pathway was increased with infection, while EIF2 signaling is the top downregulated pathway followed by eIF4/p70S6k and mTOR signaling in multiple cell types including macrophages, blood and lymphatic endothelial cells. Altogether, this transcriptomic profile highlights known recruitment of myeloid cells to lesions and recognizes a potential role for EIF2 signaling in murine L. major infection in vivo. |
format |
Article in Journal/Newspaper |
author |
Gopinath Venugopal Jordan T Bird Charity L Washam Hayden Roys Anne Bowlin Stephanie D Byrum Tiffany Weinkopff |
author_facet |
Gopinath Venugopal Jordan T Bird Charity L Washam Hayden Roys Anne Bowlin Stephanie D Byrum Tiffany Weinkopff |
author_sort |
Gopinath Venugopal |
title |
In vivo transcriptional analysis of mice infected with Leishmania major unveils cellular heterogeneity and altered transcriptomic profiling at single-cell resolution. |
title_short |
In vivo transcriptional analysis of mice infected with Leishmania major unveils cellular heterogeneity and altered transcriptomic profiling at single-cell resolution. |
title_full |
In vivo transcriptional analysis of mice infected with Leishmania major unveils cellular heterogeneity and altered transcriptomic profiling at single-cell resolution. |
title_fullStr |
In vivo transcriptional analysis of mice infected with Leishmania major unveils cellular heterogeneity and altered transcriptomic profiling at single-cell resolution. |
title_full_unstemmed |
In vivo transcriptional analysis of mice infected with Leishmania major unveils cellular heterogeneity and altered transcriptomic profiling at single-cell resolution. |
title_sort |
in vivo transcriptional analysis of mice infected with leishmania major unveils cellular heterogeneity and altered transcriptomic profiling at single-cell resolution. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2022 |
url |
https://doi.org/10.1371/journal.pntd.0010518 https://doaj.org/article/d26927c033344c0ea181b3edfa3c7df2 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 16, Iss 7, p e0010518 (2022) |
op_relation |
https://doi.org/10.1371/journal.pntd.0010518 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0010518 https://doaj.org/article/d26927c033344c0ea181b3edfa3c7df2 |
op_doi |
https://doi.org/10.1371/journal.pntd.0010518 |
container_title |
PLOS Neglected Tropical Diseases |
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16 |
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7 |
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e0010518 |
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