Molecular profiling reveals features of clinical immunity and immunosuppression in asymptomatic P. falciparum malaria
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 con...
Saved in:
Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Other Authors: | |
Format: | Article |
Published: |
2022
|
Subjects: | |
Online Access: | https://repository.li.mahidol.ac.th/handle/123456789/73035 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Institution: | Mahidol University |
id |
th-mahidol.73035 |
---|---|
record_format |
dspace |
spelling |
th-mahidol.730352022-08-04T11:12:43Z Molecular profiling reveals features of clinical immunity and immunosuppression in asymptomatic P. falciparum malaria Stephanie I. Studniberg Lisa J. Ioannidis Retno A.S. Utami Leily Trianty Yang Liao Waruni Abeysekera Connie S.N. Li-Wai-Suen Halina M. Pietrzak Julie Healer Agatha M. Puspitasari Dwi Apriyanti Farah Coutrier Jeanne R. Poespoprodjo Enny Kenangalem Benediktus Andries Pak Prayoga Novita Sariyanti Gordon K. Smyth Alan F. Cowman Ric N. Price Rintis Noviyanti Wei Shi Alexandra L. Garnham Diana S. Hansen 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 Agricultural and Biological Sciences Biochemistry, Genetics and Molecular Biology Immunology and Microbiology Mathematics 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. 2022-08-04T03:34:57Z 2022-08-04T03:34:57Z 2022-04-01 Article Molecular Systems Biology. Vol.18, No.4 (2022) 10.15252/msb.202110824 17444292 2-s2.0-85128883119 https://repository.li.mahidol.ac.th/handle/123456789/73035 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85128883119&origin=inward |
institution |
Mahidol University |
building |
Mahidol University Library |
continent |
Asia |
country |
Thailand Thailand |
content_provider |
Mahidol University Library |
collection |
Mahidol University Institutional Repository |
topic |
Agricultural and Biological Sciences Biochemistry, Genetics and Molecular Biology Immunology and Microbiology Mathematics |
spellingShingle |
Agricultural and Biological Sciences Biochemistry, Genetics and Molecular Biology Immunology and Microbiology Mathematics Stephanie I. Studniberg Lisa J. Ioannidis Retno A.S. Utami Leily Trianty Yang Liao Waruni Abeysekera Connie S.N. Li-Wai-Suen Halina M. Pietrzak Julie Healer Agatha M. Puspitasari Dwi Apriyanti Farah Coutrier Jeanne R. Poespoprodjo Enny Kenangalem Benediktus Andries Pak Prayoga Novita Sariyanti Gordon K. Smyth Alan F. Cowman Ric N. Price Rintis Noviyanti Wei Shi Alexandra L. Garnham Diana S. Hansen Molecular profiling reveals features of clinical immunity and immunosuppression in asymptomatic P. falciparum malaria |
description |
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. |
author2 |
School of Mathematics and Statistics |
author_facet |
School of Mathematics and Statistics Stephanie I. Studniberg Lisa J. Ioannidis Retno A.S. Utami Leily Trianty Yang Liao Waruni Abeysekera Connie S.N. Li-Wai-Suen Halina M. Pietrzak Julie Healer Agatha M. Puspitasari Dwi Apriyanti Farah Coutrier Jeanne R. Poespoprodjo Enny Kenangalem Benediktus Andries Pak Prayoga Novita Sariyanti Gordon K. Smyth Alan F. Cowman Ric N. Price Rintis Noviyanti Wei Shi Alexandra L. Garnham Diana S. Hansen |
format |
Article |
author |
Stephanie I. Studniberg Lisa J. Ioannidis Retno A.S. Utami Leily Trianty Yang Liao Waruni Abeysekera Connie S.N. Li-Wai-Suen Halina M. Pietrzak Julie Healer Agatha M. Puspitasari Dwi Apriyanti Farah Coutrier Jeanne R. Poespoprodjo Enny Kenangalem Benediktus Andries Pak Prayoga Novita Sariyanti Gordon K. Smyth Alan F. Cowman Ric N. Price Rintis Noviyanti Wei Shi Alexandra L. Garnham Diana S. Hansen |
author_sort |
Stephanie I. Studniberg |
title |
Molecular profiling reveals features of clinical immunity and immunosuppression in asymptomatic P. falciparum malaria |
title_short |
Molecular profiling reveals features of clinical immunity and immunosuppression in asymptomatic P. falciparum malaria |
title_full |
Molecular profiling reveals features of clinical immunity and immunosuppression in asymptomatic P. falciparum malaria |
title_fullStr |
Molecular profiling reveals features of clinical immunity and immunosuppression in asymptomatic P. falciparum malaria |
title_full_unstemmed |
Molecular profiling reveals features of clinical immunity and immunosuppression in asymptomatic P. falciparum malaria |
title_sort |
molecular profiling reveals features of clinical immunity and immunosuppression in asymptomatic p. falciparum malaria |
publishDate |
2022 |
url |
https://repository.li.mahidol.ac.th/handle/123456789/73035 |
_version_ |
1763491169371684864 |