Journal article
Human IL-10–producing Th1 cells exhibit a molecular signature distinct from Tr1 cells in malaria
CL Edwards, SS Ng, F de Labastida Rivera, D Corvino, JA Engel, MM de Oca, L Bukali, TCM Frame, PT Bunn, SB Chauhan, SS Singh, Y Wang, J Na, FH Amante, JR Loughland, MSF Soon, N Waddell, P Mukhopadhay, LT Koufariotis, RL Johnston Show all
Journal of Clinical Investigation | AMER SOC CLINICAL INVESTIGATION INC | Published : 2023
DOI: 10.1172/JCI153733
Abstract
Control of intracellular parasites responsible for malaria requires host IFN-γ+T-bet+CD4+ T cells (Th1 cells) with IL-10 produced by Th1 cells to mitigate the pathology induced by this inflammatory response. However, these IL-10–producing Th1 (induced type I regulatory [Tr1]) cells can also promote parasite persistence or impair immunity to reinfection or vaccination. Here, we identified molecular and phenotypic signatures that distinguished IL-10–Th1 cells from IL-10+Tr1 cells in Plasmodium falciparum–infected people who participated in controlled human malaria infection studies, as well as C57BL/6 mice with experimental malaria caused by P. berghei ANKA. We also identified a conserved Tr1 ..
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Awarded by Bill and Melinda Gates Foundation
Funding Acknowledgements
We thank the staff at Q-Pharm, Brisbane, Australia for collecting blood samples, and volunteers participating in clinical trials for allowing use of these samples. Thanks to Joerg Moehrle and Tim Wells and to Medicines for Malaria Venture (MMV) in Gene-va for helpful discussions and permission to participate in CHMI studies. We thank the QIMR Berghofer Animal Facility and Flow Cytometry Facility for their help. We also thank Chris Jeans (QB3 MacroLab, University of California, Berkeley) , for supplying puri-fied Cas9-NLS protein for gene editing experiments. This work was made possible through Queensland State Government fund-ing, grants and fellowships from the National Health and Medical Research Council of Australia (NHMRC; grant numbers 1132975 and 1154265) . Funding for the CHMI studies was provided by MMV from grants awarded by the Wellcome Trust and Bill and Melinda Gates Foundation. R. Kumar receives funding from an Indian Council of Medical Research (ICMR) grant and BHU-IoE seed grant. Authors were also supported by Australian Postgradu-ate Award through the University of Queensland, School of Med-icine, Griffith University, School of Natural Sciences, an Indian DST INSPIRE Scholarship, an Indian Council for Scientific and Industrial Research Fellowship, and an INSPIRE Fellowship.