Molecular profiling reveals features of clinical immunity and immunosuppression in asymptomatic P. falciparum malaria

Studniberg, SI; Ioannidis, LJ; Utami, RAS; Trianty, L; Liao, Y; Abeysekera, W; Li-Wai-Suen, CSN; Pietrzak, HM; Healer, J; Puspitasari, AM; Apriyanti, D; Coutrier, F; Poespoprodjo, JR; Kenangalem, E; Andries, B; Prayoga, P; Sariyanti, N; Smyth, GK; Cowman, AF; Price, RN; Noviyanti, R; Shi, W; Garnham, AL; Hansen, DS

Author(s): Studniberg, SI; Ioannidis, LJ; Utami, RAS; Trianty, L; Liao, Y; Abeysekera, W; Li-Wai-Suen, CSN; Pietrzak, HM; Healer, J; Puspitasari, AM; Apriyanti, D; Coutrier, F; Poespoprodjo, JR; Kenangalem, E; Andries, B; Prayoga, P; Sariyanti, N; Smyth, GK; Cowman, AF; Price, RN; Noviyanti, R; Shi, W; Garnham, AL; Hansen, DS;
Details: Publication Year 2022-04,Volume 18,Issue #4,Page e10824
Journal Title: Molecular Systems Biology
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 T(H2) 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.
Publisher: EMBO Press
Keywords: Adult; Asymptomatic Infections; CTLA-4 Antigen; Humans; Immunosuppression Therapy; *Malaria, Falciparum/genetics/parasitology; *Parasitemia; Plasmodium falciparum; P. falciparum; asymptomatic infection; immunity; immunosuppression; malaria
Research Division(s): Bioinformatics; Infectious Diseases And Immune Defence
PubMed ID: 35475529
Publisher's Version: https://doi.org/10.15252/msb.202110824
Open Access at Publisher's Site: https://doi.org/10.15252/msb.202110824
NHMRC Grants: NHMRC/1058665, NHMRC/1137989,
Terms of Use/Rights Notice: Refer to copyright notice on published article.
Documents: Molecular Systems Biology - 2022 - Studniberg - Molecular profiling reveals features of clinical immunity and.pdf - (6.61MB, application/pdf)

Creation Date: 2022-05-03 09:18:44

Last Modified: 2022-07-13 02:48:26