Dramatic transcriptomic differences in Macaca mulatta and Macaca fascicularis with Plasmodium knowlesi infections.
Animals
Biological Evolution
Biomarkers
Computational Biology
/ methods
Gene Expression Profiling
Gene Expression Regulation
Host-Parasite Interactions
/ genetics
Macaca fascicularis
Macaca mulatta
Malaria
/ veterinary
Molecular Sequence Annotation
Monkey Diseases
/ genetics
Plasmodium knowlesi
Signal Transduction
Species Specificity
Transcriptome
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
30 09 2021
30 09 2021
Historique:
received:
03
03
2021
accepted:
30
08
2021
entrez:
1
10
2021
pubmed:
2
10
2021
medline:
29
12
2021
Statut:
epublish
Résumé
Plasmodium knowlesi, a model malaria parasite, is responsible for a significant portion of zoonotic malaria cases in Southeast Asia and must be controlled to avoid disease severity and fatalities. However, little is known about the host-parasite interactions and molecular mechanisms in play during the course of P. knowlesi malaria infections, which also may be relevant across Plasmodium species. Here we contrast P. knowlesi sporozoite-initiated infections in Macaca mulatta and Macaca fascicularis using whole blood RNA-sequencing and transcriptomic analysis. These macaque hosts are evolutionarily close, yet malaria-naïve M. mulatta will succumb to blood-stage infection without treatment, whereas malaria-naïve M. fascicularis controls parasitemia without treatment. This comparative analysis reveals transcriptomic differences as early as the liver phase of infection, in the form of signaling pathways that are activated in M. fascicularis, but not M. mulatta. Additionally, while most immune responses are initially similar during the acute stage of the blood infection, significant differences arise subsequently. The observed differences point to prolonged inflammation and anti-inflammatory effects of IL10 in M. mulatta, while M. fascicularis undergoes a transcriptional makeover towards cell proliferation, consistent with its recovery. Together, these findings suggest that timely detection of P. knowlesi in M. fascicularis, coupled with control of inflammation while initiating the replenishment of key cell populations, helps contain the infection. Overall, this study points to specific genes and pathways that could be investigated as a basis for new drug targets that support recovery from acute malaria.
Identifiants
pubmed: 34593836
doi: 10.1038/s41598-021-98024-6
pii: 10.1038/s41598-021-98024-6
pmc: PMC8484567
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
19519Subventions
Organisme : CLC NIH HHS
ID : C0000008
Pays : United States
Organisme : NIAID NIH HHS
ID : HHSN272201200031C
Pays : United States
Organisme : NIH HHS
ID : P51 OD011132
Pays : United States
Informations de copyright
© 2021. The Author(s).
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