Mapping T cell activation and differentiation at single cell resolution in naive hosts infected with<i>Plasmodium vivax</i>
The biology ofPlasmodium vivaxis markedly different to that ofP. falciparum; how this shapes the immune response to infection remains unclear. To address this shortfall, we inoculated human volunteers with a clonal field isolate ofP. vivaxand tracked their response through infection and convalescence. High dimensional protein and RNA-seq data show thatP. vivaxtriggers an acute phase response that shares remarkable overlap with that ofP. falciparum, suggesting a hardwired emergency myeloid response that does not discriminate parasite species. We then used cytometry by time of flight to analyse the fate and function of innate-like and adaptive T cells; these data show thatP. vivaxcan activate up to one quarter of the entire T cell compartment. Heterogeneous effector memory-like CD4+T cells dominate this extraordinary response and phenotypic analysis reveals unexpected features of terminal differentiation that are normally associated with cytotoxicity and autoinflammatory disease. In line with this observation, we found that CD4+T cell activation coincides with collateral tissue damage and liver injury. Finally, comparative analyses demonstrate thatP. falciparumdrives T cell activation far in excess ofP. vivax, which may partially explain why falciparum malaria more frequently causes severe disease..
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
bioRxiv.org - (2024) vom: 23. Apr. Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bach, Florian A. [VerfasserIn] |
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| doi: |
10.1101/2021.03.22.21252810 |
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| PPN (Katalog-ID): |
XBI020201303 |
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| 520 | |a The biology ofPlasmodium vivaxis markedly different to that ofP. falciparum; how this shapes the immune response to infection remains unclear. To address this shortfall, we inoculated human volunteers with a clonal field isolate ofP. vivaxand tracked their response through infection and convalescence. High dimensional protein and RNA-seq data show thatP. vivaxtriggers an acute phase response that shares remarkable overlap with that ofP. falciparum, suggesting a hardwired emergency myeloid response that does not discriminate parasite species. We then used cytometry by time of flight to analyse the fate and function of innate-like and adaptive T cells; these data show thatP. vivaxcan activate up to one quarter of the entire T cell compartment. Heterogeneous effector memory-like CD4+T cells dominate this extraordinary response and phenotypic analysis reveals unexpected features of terminal differentiation that are normally associated with cytotoxicity and autoinflammatory disease. In line with this observation, we found that CD4+T cell activation coincides with collateral tissue damage and liver injury. Finally, comparative analyses demonstrate thatP. falciparumdrives T cell activation far in excess ofP. vivax, which may partially explain why falciparum malaria more frequently causes severe disease. | ||
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| 700 | 1 | |a Themistocleous, Yrene |e verfasserin |4 aut | |
| 700 | 1 | |a Rawlinson, Thomas A. |e verfasserin |4 aut | |
| 700 | 1 | |a Kemp, Alison |e verfasserin |4 aut | |
| 700 | 1 | |a Silk, Sarah E. |e verfasserin |4 aut | |
| 700 | 1 | |a Barrett, Jordan R. |e verfasserin |4 aut | |
| 700 | 1 | |a Edwards, Nick J. |e verfasserin |4 aut | |
| 700 | 1 | |a Ivens, Alasdair |e verfasserin |4 aut | |
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| 700 | 1 | |a Spence, Philip J. |e verfasserin |0 (orcid)0000-0002-5506-2773 |4 aut | |
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