Journal article
Interplay between liver and blood stages of Plasmodium infection dictates malaria severity via γδ T cells and IL-17-promoted stress erythropoiesis
ÂF Chora, S Marques, JL Gonçalves, P Lima, D Gomes da Costa, D Fernandez-Ruiz, MI Marreiros, P Ruivo, T Carvalho, RM Ribeiro, K Serre, WR Heath, B Silva-Santos, AT Tate, MM Mota
Immunity | Published : 2023
Abstract
Plasmodium replicates within the liver prior to reaching the bloodstream and infecting red blood cells. Because clinical manifestations of malaria only arise during the blood stage of infection, a perception exists that liver infection does not impact disease pathology. By developing a murine model where the liver and blood stages of infection are uncoupled, we showed that the integration of signals from both stages dictated mortality outcomes. This dichotomy relied on liver stage-dependent activation of Vγ4+ γδ T cells. Subsequent blood stage parasite loads dictated their cytokine profiles, where low parasite loads preferentially expanded IL-17-producing γδ T cells. IL-17 drove extra-medull..
View full abstractRelated Projects (2)
Grants
Awarded by Alfred P. Sloan Foundation
Funding Acknowledgements
We would like to acknowledge Freddy Frischknecht (Integrative Parasitology Center for Infectious Diseases, Heidelberg) for providing the Plasmodium berghei lisp2-parasite line, Immo Prinz (Hannover Medical School, Hannover) for providing genetically modified mouse lines, Ana Parreira (iMM-JLA, Portugal) and Geoff McFadden's lab (School of BioSciences, University of Melbourne, Australia) for mosquito rearing and infection with Plasmodium parasites, Helena Pinheiro (iMM-JLA, Portugal) for assistance with graphical design, Ines Bento and Miguel Prudencio for critically reviewing this manuscript, and the Flow Cytometry and Rodent Facilities teams (iMM-JLA, Portugal) for their assistance. Work at iMM-JLA was supported by Fundacao para a Ciencia e a Tecnologia. Portugal (PTDC/MED-IMU/28664/2017) and the "La caixa"Banking Foundation, Spain (HR17-00264-PoEMM) grants attributed to A.F.C. and M.M.M., respectively. Work at the Department of Microbiology and Immunology, The University of Melbourne, Australia, was funded by the National Health and Medical Research Council, Australia (1113293, 1154457) and the Australian Research Council, Australia (CE140100011). A.F.C., S.M., J.L.G., M.I.M., R.M.R., and K.S. were supported by Fundacao para a Ciencia e a Tecnologia, Portugal (DL57/2016/CP1451/CT0004, DL57/2016/CP1451/CT0010, PD/BD/139053/2018, PD/BD/135454/2017, PTDC/MAT-APL/31602/2017, and CEECIND/00697/2018, respectively), P.L. was supported by Conselho Nacional de Desenvolvimento Cientifico e Tenologico, Brazil (SN/CGEFO/CNPQ 201801/2015-9), and A.T.T. was supported in part by Alfred P. Sloan Foundation Fellowship (FG-2020-12949).