1. Infection-induced plasmablasts are a nutrient sink that impairs humoral immunity to malaria.
- Author
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Vijay R, Guthmiller JJ, Sturtz AJ, Surette FA, Rogers KJ, Sompallae RR, Li F, Pope RL, Chan JA, de Labastida Rivera F, Andrew D, Webb L, Maury WJ, Xue HH, Engwerda CR, McCarthy JS, Boyle MJ, and Butler NS
- Subjects
- Adolescent, Adult, Amino Acids administration & dosage, Amino Acids metabolism, Animals, Antibodies, Protozoan blood, Antibodies, Protozoan immunology, Antibodies, Protozoan metabolism, Antimalarials administration & dosage, DNA, Protozoan isolation & purification, Disease Models, Animal, Germinal Center cytology, Germinal Center immunology, Germinal Center metabolism, Host-Parasite Interactions immunology, Humans, Malaria blood, Malaria drug therapy, Malaria parasitology, Mice, Mice, Transgenic, Middle Aged, Nutrients metabolism, Plasma Cells immunology, Plasma Cells parasitology, Plasmodium falciparum genetics, Plasmodium falciparum isolation & purification, Proof of Concept Study, Young Adult, Immunity, Humoral, Malaria immunology, Plasma Cells metabolism, Plasmodium falciparum immunology
- 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 the metabolic constraints imposed by plasmablasts and enhanced parasite clearance and the formation of protective humoral immune memory responses. Thus, our studies not only challenge the current model describing the role and function of blood-stage Plasmodium-induced plasmablasts but they also reveal new targets and strategies to improve anti-Plasmodium humoral immunity.
- Published
- 2020
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