Journal article
Sting activation promotes autologous type i interferon–dependent development of type 1 regulatory t cells during malaria
Y Wang, F De Labastida Rivera, CL Edwards, TCM Frame, JA Engel, L Bukali, J Na, SS Ng, D Corvino, MM De Oca, PT Bunn, MSF Soon, D Andrew, JR Loughland, J Zhang, FH Amante, BE Barber, JS McCarthy, JA Lopez, MJ Boyle Show all
Journal of Clinical Investigation | AMER SOC CLINICAL INVESTIGATION INC | Published : 2023
DOI: 10.1172/JCI169417
Abstract
The development of highly effective malaria vaccines and improvement of drug-treatment protocols to boost antiparasitic immunity are critical for malaria elimination. However, the rapid establishment of parasite-specific immune regulatory networks following exposure to malaria parasites hampers these efforts. Here, we identified stimulator of interferon genes (STING) as a critical mediator of type I interferon production by CD4+ T cells during blood-stage Plasmodium falciparum infection. The activation of STING in CD4+ T cells by cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) stimulated IFNB gene transcription, which promoted development of IL-10– and IFN-γ–coproducing CD4+ T..
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Funding Acknowledgements
We would like to thank the volunteers who participated in the study, members of the Clinical Malaria Laboratory at QIMR, and the clinical study team at Q-Pharm (Brisbane, Australia) who conducted the CHMI trial. We thank staff of the QIMR Berghofer Flow Cytometry Laboratory for assistance and staff of the QIMR Animal Facility for animal husbandry. We thank Nicola Waddell, Ross Loufariotis, and Rebecca Johnston for bioinformatics and computational support. Thanks to Joerg Moehrle and Tim Wells at Medicines for Malaria Venture (MMV) for collaborating on human CHMI studies. Funding for the CHMI platform came from Australia and the UK. We also thank Chris Jeans for supplying purified Cas9-NLS protein for gene-editing experiments. This work was made possible through the Queensland state government, grants and fellowships from the National Health and Medical Research Council of Australia (NHMRC) (grant numbers 1037304, 1058685, 1132975, 1154265, and 1141632) , Australian Post-Graduate Awards through Griffith University, School of Natural Sciences, and the University of Queensland, School of Medicine.