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; Michelle J. Boyle

doi:10.1038/s41467-023-43181-7

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, Michelle J. Boyle

Menzies School of Health Research

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Article number	7387
Pages (from-to)	1-22
Number of pages	22
Journal	Nature Communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-43181-7
Publication status	Published - Dec 2023

Bibliographical note

Funding Information:
We thank all the participants and parents of guardians involved in the clinical studies, along with the Malaysian Ministry of Health hospital directors and clinical staff at Kudat, Kota Marudu and Pitas district hospitals and at Queen Elizabeth Hospital, Kota Kinabalu. We thank support staff in QIMR Flow Cytometry and Imaging Facility, QIMR Sample Processing and Sequencing Service, and Dr. Jessica Engel for laboratory support. This work was supported by the National Health and Medical Research Council of Australia (Career Development Fellowship 1141632 to M.J.B., Ideas Grant 1181932 to M.J.B., Program Grants 1037304 and 1132975 to NMA, Senior Principal Research Fellowship 1135820 to NMA and by The Australian Centre of Research Excellence in Malaria Elimination Seed Grant to J.R.L.

Funding Information:
We thank all the participants and parents of guardians involved in the clinical studies, along with the Malaysian Ministry of Health hospital directors and clinical staff at Kudat, Kota Marudu and Pitas district hospitals and at Queen Elizabeth Hospital, Kota Kinabalu. We thank support staff in QIMR Flow Cytometry and Imaging Facility, QIMR Sample Processing and Sequencing Service, and Dr. Jessica Engel for laboratory support. This work was supported by the National Health and Medical Research Council of Australia (Career Development Fellowship 1141632 to M.J.B., Ideas Grant 1181932 to M.J.B., Program Grants 1037304 and 1132975 to NMA, Senior Principal Research Fellowship 1135820 to NMA and by The Australian Centre of Research Excellence in Malaria Elimination Seed Grant to J.R.L.

Publisher Copyright:
© 2023, The Author(s).

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Dooley, N. L., Chabikwa, T. G., Pava, Z., Loughland, J. R., Hamelink, J., Berry, K., Andrew, D., Soon, M. S. F., SheelaNair, A., Piera, K. A., William, T., Barber, B. E., Grigg, M. J., Engwerda, C. R., Lopez, J. A., Anstey, N. M., & Boyle, M. J. (2023). Single cell transcriptomics shows that malaria promotes unique regulatory responses across multiple immune cell subsets. Nature Communications, 14(1), 1-22. Article 7387. https://doi.org/10.1038/s41467-023-43181-7

@article{260da544c2a7497caf3dc26c9d86de5f,

title = "Single cell transcriptomics shows that malaria promotes unique regulatory responses across multiple immune cell subsets",

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.",

author = "Dooley, \{Nicholas L.\} and Chabikwa, \{Tinashe G.\} and Zuleima Pava and Loughland, \{Jessica R.\} and Julianne Hamelink and Kiana Berry and Dean Andrew and Soon, \{Megan S.F.\} and Arya SheelaNair and Piera, \{Kim A.\} and Timothy William and Barber, \{Bridget E.\} and Grigg, \{Matthew J.\} and Engwerda, \{Christian R.\} and Lopez, \{J. Alejandro\} and Anstey, \{Nicholas M.\} and Boyle, \{Michelle J.\}",

note = "Funding Information: We thank all the participants and parents of guardians involved in the clinical studies, along with the Malaysian Ministry of Health hospital directors and clinical staff at Kudat, Kota Marudu and Pitas district hospitals and at Queen Elizabeth Hospital, Kota Kinabalu. We thank support staff in QIMR Flow Cytometry and Imaging Facility, QIMR Sample Processing and Sequencing Service, and Dr. Jessica Engel for laboratory support. This work was supported by the National Health and Medical Research Council of Australia (Career Development Fellowship 1141632 to M.J.B., Ideas Grant 1181932 to M.J.B., Program Grants 1037304 and 1132975 to NMA, Senior Principal Research Fellowship 1135820 to NMA and by The Australian Centre of Research Excellence in Malaria Elimination Seed Grant to J.R.L. Funding Information: We thank all the participants and parents of guardians involved in the clinical studies, along with the Malaysian Ministry of Health hospital directors and clinical staff at Kudat, Kota Marudu and Pitas district hospitals and at Queen Elizabeth Hospital, Kota Kinabalu. We thank support staff in QIMR Flow Cytometry and Imaging Facility, QIMR Sample Processing and Sequencing Service, and Dr. Jessica Engel for laboratory support. This work was supported by the National Health and Medical Research Council of Australia (Career Development Fellowship 1141632 to M.J.B., Ideas Grant 1181932 to M.J.B., Program Grants 1037304 and 1132975 to NMA, Senior Principal Research Fellowship 1135820 to NMA and by The Australian Centre of Research Excellence in Malaria Elimination Seed Grant to J.R.L. Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = dec,

doi = "10.1038/s41467-023-43181-7",

language = "English",

volume = "14",

pages = "1--22",

journal = "Nature Communications",

issn = "2041-1723",

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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 2023, 'Single cell transcriptomics shows that malaria promotes unique regulatory responses across multiple immune cell subsets', Nature Communications, vol. 14, no. 1, 7387, pp. 1-22. https://doi.org/10.1038/s41467-023-43181-7

TY - JOUR

T1 - Single cell transcriptomics shows that malaria promotes unique regulatory responses across multiple immune cell subsets

AU - Dooley, Nicholas L.

AU - Chabikwa, Tinashe G.

AU - Pava, Zuleima

AU - Loughland, Jessica R.

AU - Hamelink, Julianne

AU - Berry, Kiana

AU - Andrew, Dean

AU - Soon, Megan S.F.

AU - SheelaNair, Arya

AU - Piera, Kim A.

AU - William, Timothy

AU - Barber, Bridget E.

AU - Grigg, Matthew J.

AU - Engwerda, Christian R.

AU - Lopez, J. Alejandro

AU - Anstey, Nicholas M.

AU - Boyle, Michelle J.

N1 - Funding Information: We thank all the participants and parents of guardians involved in the clinical studies, along with the Malaysian Ministry of Health hospital directors and clinical staff at Kudat, Kota Marudu and Pitas district hospitals and at Queen Elizabeth Hospital, Kota Kinabalu. We thank support staff in QIMR Flow Cytometry and Imaging Facility, QIMR Sample Processing and Sequencing Service, and Dr. Jessica Engel for laboratory support. This work was supported by the National Health and Medical Research Council of Australia (Career Development Fellowship 1141632 to M.J.B., Ideas Grant 1181932 to M.J.B., Program Grants 1037304 and 1132975 to NMA, Senior Principal Research Fellowship 1135820 to NMA and by The Australian Centre of Research Excellence in Malaria Elimination Seed Grant to J.R.L. Funding Information: We thank all the participants and parents of guardians involved in the clinical studies, along with the Malaysian Ministry of Health hospital directors and clinical staff at Kudat, Kota Marudu and Pitas district hospitals and at Queen Elizabeth Hospital, Kota Kinabalu. We thank support staff in QIMR Flow Cytometry and Imaging Facility, QIMR Sample Processing and Sequencing Service, and Dr. Jessica Engel for laboratory support. This work was supported by the National Health and Medical Research Council of Australia (Career Development Fellowship 1141632 to M.J.B., Ideas Grant 1181932 to M.J.B., Program Grants 1037304 and 1132975 to NMA, Senior Principal Research Fellowship 1135820 to NMA and by The Australian Centre of Research Excellence in Malaria Elimination Seed Grant to J.R.L. Publisher Copyright: © 2023, The Author(s).

PY - 2023/12

Y1 - 2023/12

N2 - 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.

AB - 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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DO - 10.1038/s41467-023-43181-7

M3 - Article

C2 - 37968278

AN - SCOPUS:85176796083

SN - 2041-1723

VL - 14

SP - 1

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JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 7387

ER -

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

Abstract

Bibliographical note

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