Single cell transcriptomics shows that malaria promotes unique regulatory responses across multiple immune cell subsets

Nicholas L. Dooley, Tinashe G. Chabikwa, Zuleima Pava, Jessica R. Loughland, Julianne Hamelink, Kiana Berry, Dean Andrew, Megan S. F. Soon, Arya SheelaNair, Kim A. Piera, Timothy William, Bridget E. Barber, Matthew J. Grigg, Christian R. Engwerda, J. Alejandro Lopez, Nicholas M. Anstey and Michelle J. Boyle ()
Additional contact information
Nicholas L. Dooley: QIMR Berghofer Medical Research Institute
Tinashe G. Chabikwa: QIMR Berghofer Medical Research Institute
Zuleima Pava: QIMR Berghofer Medical Research Institute
Jessica R. Loughland: QIMR Berghofer Medical Research Institute
Julianne Hamelink: QIMR Berghofer Medical Research Institute
Kiana Berry: QIMR Berghofer Medical Research Institute
Dean Andrew: QIMR Berghofer Medical Research Institute
Megan S. F. Soon: QIMR Berghofer Medical Research Institute
Arya SheelaNair: QIMR Berghofer Medical Research Institute
Kim A. Piera: Charles Darwin University
Timothy William: Infectious Diseases Society Kota Kinabalu Sabah-Menzies School of Health Research Program
Bridget E. Barber: QIMR Berghofer Medical Research Institute
Matthew J. Grigg: Charles Darwin University
Christian R. Engwerda: QIMR Berghofer Medical Research Institute
J. Alejandro Lopez: QIMR Berghofer Medical Research Institute
Nicholas M. Anstey: Charles Darwin University
Michelle J. Boyle: QIMR Berghofer Medical Research Institute

Nature Communications, 2023, vol. 14, issue 1, 1-22

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-43181-7

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