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Cited by 26Research on Leishmaniasis StudiesLeprosy Research and TreatmentParasitic Diseases Research and Treatment

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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Venugopal, Gopinath, Bird, Jordan T., Washam, Charity L., Roys, Hayden, Bowlin, Anne, Byrum, Stephanie D., Weinkopff, Tiffany·2022·PLOS Neglected Tropical Diseases
DOI 10.1371/journal.pntd.0010518PMC PMC9286232
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Abstract

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.

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Cited by

Sorted by citations

Authors
Venugopal, G., Bird, J. T., Washam, C. L., Roys, H., Bowlin, A., Byrum, S. D., & Weinkopff, T.
Affiliations
  • University of Arkansas for Medical Sciences (US)
  • Arkansas Children's Research Institute (US)
Corresponding author
  • Byrum, Stephanie D.
  • Weinkopff, Tiffany
ORCID
Venue
PLOS Neglected Tropical Diseases
Publisher
Public Library of Science (PLoS)
Published
2022-07-05
Volume
16
Issue
7
Pages
e0010518
ISSN
  • 1935-2727 (ISSN-L)
  • 1935-2735
DOI
10.1371/journal.pntd.0010518
PMC
PMC9286232
OpenAlex
W4283825795
Cited by
26
References
3
Citations by year
2026: 5 · 2025: 7 · 2024: 7 · 2023: 6 · 2022: 1
FWCI
4.64
Type
journal article
Language
en
Update notices
new_version (2022-07-15)
Open access
Licence
Locations
  • PLoS neglected tropical diseases (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institute of General Medical Sciences (P20-GM103625, P20GM121293)
  • Oak Ridge Associated Universities (Ralph E. Powe Junior Faculty Enhancement Award)
  • National Center for Advancing Translational Sciences (UL1-TR003107)
  • National Science Foundation (OIA-1946391)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Research on Leishmaniasis Studies
  • Health Sciences › Medicine › Infectious Diseases › Leprosy Research and Treatment
  • Health Sciences › Medicine › Infectious Diseases › Parasitic Diseases Research and Treatment
Keywords
Leishmania major, cutaneous leishmaniasis, host immune response, single-cell transcriptomics, antigen processing and presentation, EIF2 signaling, mTOR signaling, macrophages, inflammatory monocytes, myeloid cell recruitment, skin transcriptome, mouse model
MeSH terms
Animals, Eukaryotic Initiation Factor-2, Leishmania major, Gene Expression Profiling, Endothelial Cells, Mice, Transcriptome

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