Journal article
Infection-induced plasmablasts are a nutrient sink that impairs humoral immunity to malaria
Rahul Vijay, Jenna J Guthmiller, Alexandria J Sturtz, Fionna A Surette, Kai J Rogers, Ramakrishna R Sompallae, Fengyin Li, Rosemary L Pope, Jo-Anne Chan, Fabian de Labastida Rivera, Dean Andrew, Lachlan Webb, Wendy J Maury, Hai-Hui Xue, Christian R Engwerda, James S McCarthy, Michelle J Boyle, Noah S Butler
Nature Immunology | Nature Research | Published : 2020
Abstract
Plasmodium parasite–specific antibodies are critical for protection against malaria, yet the development of long-lived and effective humoral immunity against Plasmodium takes many years and multiple rounds of infection and cure. Here, we report that the rapid development of short-lived plasmablasts during experimental malaria unexpectedly hindered parasite control by impeding germinal center responses. Metabolic hyperactivity of plasmablasts resulted in nutrient deprivation of the germinal center reaction, limiting the generation of memory B cell and long-lived plasma cell responses. Therapeutic administration of a single amino acid to experimentally infected mice was sufficient to overcome ..
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Grants
Awarded by NCI
Awarded by National Center for Research Resources of the NIH
Awarded by American Heart Association
Awarded by NIH
Awarded by Veteran Affairs BLR&D Merit Review Program
Awarded by NHMRC Senior Research Fellowship
Awarded by NHMRC Program grant
Awarded by NHMRC Practitioner Fellowship
Awarded by NHMRC Career Development Fellowship
Awarded by NHMRC Project Grant
Funding Acknowledgements
We thank members of the University of Iowa Butler laboratory for assistance and helpful discussions, F. Lund (University of Alabama, Birmingham) for the mu S<SUP>-/-</SUP> mice, T. Honjo (Kyoto University) for the Aicda<SUP>-/-</SUP> mice, T. Waldschmidt (University of Iowa) for the clone MR-1 antibody, J. Harty and S. Perlman (University of Iowa) for critical reading of the manuscript and helpful discussions, A. Pewa, E. Taylor and A. Rauckhorst (University of Iowa) for assistance with the metabolic measurements, G. Beuttener and B. Wagner (University of Iowa) for the metabolic flux assays, and members of the University of Iowa Flow Cytometry Facility for cell sorting. The research reported in this publication was supported by the NCI (grant number P30CA086862) and the National Center for Research Resources of the NIH (grant number S10OD016199). J.J.G. was supported by a Predoctoral Fellowship from the American Heart Association (grant number 16PRE27660002). F.A.S. was supported by the NIH (grant number T32 AI007485). K.J.R. was supported by the NIH (T32 GM067795). W.J.M. was supported by the NIH (grant numbers AI134733 and AI139902). H.-H.X. was supported by the NIH (grant numbers AI121080 and AI139874) and the Veteran Affairs BLR&D Merit Review Program (BX002903). C.R.E. was supported by an NHMRC Senior Research Fellowship (grant number 1154265) and an NHMRC Program grant (grant number 1132975). J.S.M. was supported by an NHMRC Program grant (grant number 1132975) and an NHMRC Practitioner Fellowship (grant number 1135955). M.J.B. was supported by an NHMRC Career Development Fellowship (grant number 1141632) and an NHMRC Project Grant (grant number 1141278). N.S.B. was supported by the NIH (grant numbers AI125446, AI127481 and AI139902). We thank the participants involved in the malaria VISs, Q-Pharm staff and the Medicine for Malaria Venture for funding the clinical trials.