Single cell transcriptomics shows that malaria promotes unique regulatory responses across multiple immune cell subsets
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Chabikwa, Tinashe G
Pava, Zuleima
Loughland, Jessica R
Hamelink, Julianne
Berry, Kiana
Andrew, Dean
Soon, Megan SF
SheelaNair, Arya
Piera, Kim A
William, Timothy
Barber, Bridget E
Grigg, Matthew J
Engwerda, Christian R
Lopez, J Alejandro
et al.
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Abstract
Plasmodium falciparum malaria drives immunoregulatory responses across multiple cell subsets, which protects from immunopathogenesis, but also hampers the development of effective anti-parasitic immunity. Understanding malaria induced tolerogenic responses in specific cell subsets may inform development of strategies to boost protective immunity during drug treatment and vaccination. Here, we analyse the immune landscape with single cell RNA sequencing during P. falciparum malaria. We identify cell type specific responses in sub-clustered major immune cell types. Malaria is associated with an increase in immunosuppressive monocytes, alongside NK and γδ T cells which up-regulate tolerogenic markers. IL-10-producing Tr1 CD4 T cells and IL-10-producing regulatory B cells are also induced. Type I interferon responses are identified across all cell types, suggesting Type I interferon signalling may be linked to induction of immunoregulatory networks during malaria. These findings provide insights into cell-specific and shared immunoregulatory changes during malaria and provide a data resource for further analysis.
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Nature Communications
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14
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© The Author(s) 2023. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
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Virology
Immunology
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Dooley, NL; Chabikwa, TG; Pava, Z; Loughland, JR; Hamelink, J; Berry, K; Andrew, D; Soon, MSF; SheelaNair, A; Piera, KA; William, T; Barber, BE; Grigg, MJ; Engwerda, CR; Lopez, JA; Anstey, NM; Boyle, MJ, Single cell transcriptomics shows that malaria promotes unique regulatory responses across multiple immune cell subsets, Nature Communications, 2023, 14, pp. 7387