Molecular profiling reveals features of clinical immunity and immunosuppression in asymptomatic P. falciparum malaria
4
Issued Date
2022-04-01
Resource Type
eISSN
17444292
Scopus ID
2-s2.0-85128883119
Pubmed ID
35475529
Journal Title
Molecular Systems Biology
Volume
18
Issue
4
Rights Holder(s)
SCOPUS
Bibliographic Citation
Molecular Systems Biology Vol.18 No.4 (2022)
Suggested Citation
Studniberg S.I., Ioannidis L.J., Utami R.A.S., Trianty L., Liao Y., Abeysekera W., Li-Wai-Suen C.S.N., Pietrzak H.M., Healer J., Puspitasari A.M., Apriyanti D., Coutrier F., Poespoprodjo J.R., Kenangalem E., Andries B., Prayoga P., Sariyanti N., Smyth G.K., Cowman A.F., Price R.N., Noviyanti R., Shi W., Garnham A.L., Hansen D.S. Molecular profiling reveals features of clinical immunity and immunosuppression in asymptomatic P. falciparum malaria. Molecular Systems Biology Vol.18 No.4 (2022). doi:10.15252/msb.202110824 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/83285
Title
Molecular profiling reveals features of clinical immunity and immunosuppression in asymptomatic P. falciparum malaria
Author(s)
Studniberg S.I.
Ioannidis L.J.
Utami R.A.S.
Trianty L.
Liao Y.
Abeysekera W.
Li-Wai-Suen C.S.N.
Pietrzak H.M.
Healer J.
Puspitasari A.M.
Apriyanti D.
Coutrier F.
Poespoprodjo J.R.
Kenangalem E.
Andries B.
Prayoga P.
Sariyanti N.
Smyth G.K.
Cowman A.F.
Price R.N.
Noviyanti R.
Shi W.
Garnham A.L.
Hansen D.S.
Ioannidis L.J.
Utami R.A.S.
Trianty L.
Liao Y.
Abeysekera W.
Li-Wai-Suen C.S.N.
Pietrzak H.M.
Healer J.
Puspitasari A.M.
Apriyanti D.
Coutrier F.
Poespoprodjo J.R.
Kenangalem E.
Andries B.
Prayoga P.
Sariyanti N.
Smyth G.K.
Cowman A.F.
Price R.N.
Noviyanti R.
Shi W.
Garnham A.L.
Hansen D.S.
Author's Affiliation
School of Mathematics and Statistics
Olivia Newton-John Cancer Research Institute
Eijkman Institute for Molecular Biology
Walter and Eliza Hall Institute of Medical Research
University of Melbourne
Menzies School of Health Research
Mahidol University
Nuffield Department of Medicine
Papuan Health and Community Development Foundation
Olivia Newton-John Cancer Research Institute
Eijkman Institute for Molecular Biology
Walter and Eliza Hall Institute of Medical Research
University of Melbourne
Menzies School of Health Research
Mahidol University
Nuffield Department of Medicine
Papuan Health and Community Development Foundation
Other Contributor(s)
Abstract
Clinical immunity to P. falciparum malaria is non-sterilizing, with adults often experiencing asymptomatic infection. Historically, asymptomatic malaria has been viewed as beneficial and required to help maintain clinical immunity. Emerging views suggest that these infections are detrimental and constitute a parasite reservoir that perpetuates transmission. To define the impact of asymptomatic malaria, we pursued a systems approach integrating antibody responses, mass cytometry, and transcriptional profiling of individuals experiencing symptomatic and asymptomatic P. falciparum infection. Defined populations of classical and atypical memory B cells and a TH2 cell bias were associated with reduced risk of clinical malaria. Despite these protective responses, asymptomatic malaria featured an immunosuppressive transcriptional signature with upregulation of pathways involved in the inhibition of T-cell function, and CTLA-4 as a predicted regulator in these processes. As proof of concept, we demonstrated a role for CTLA-4 in the development of asymptomatic parasitemia in infection models. The results suggest that asymptomatic malaria is not innocuous and might not support the induction of immune processes to fully control parasitemia or efficiently respond to malaria vaccines.