Journal article
Infection-induced plasmablasts are a nutrient sink that impairs humoral immunity to malaria
Nature immunology, Vol.21(7), pp.790-801
07/2020
DOI: 10.1038/s41590-020-0678-5
PMCID: PMC7316608
PMID: 32424361
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.
Details
- Title: Subtitle
- Infection-induced plasmablasts are a nutrient sink that impairs humoral immunity to malaria
- Creators
- Rahul Vijay - University of IowaJenna J Guthmiller - University of ChicagoAlexandria J Sturtz - University of IowaFionna A Surette - University of IowaKai J Rogers - University of IowaRamakrishna R Sompallae - University of IowaFengyin Li - University of IowaRosemary L Pope - University of Oklahoma Health Sciences CenterJo-Anne Chan - Burnet InstituteFabian de Labastida Rivera - QIMR Berghofer Medical Research InstituteDean Andrew - QIMR Berghofer Medical Research InstituteLachlan Webb - QIMR Berghofer Medical Research InstituteWendy J Maury - University of IowaHai-Hui Xue - University of IowaChristian R Engwerda - QIMR Berghofer Medical Research InstituteJames S McCarthy - QIMR Berghofer Medical Research InstituteMichelle J Boyle - Burnet InstituteNoah S Butler - University of Oklahoma Health Sciences Center
- Resource Type
- Journal article
- Publication Details
- Nature immunology, Vol.21(7), pp.790-801
- DOI
- 10.1038/s41590-020-0678-5
- PMID
- 32424361
- PMCID
- PMC7316608
- NLM abbreviation
- Nat Immunol
- ISSN
- 1529-2908
- eISSN
- 1529-2916
- Grant note
- T32 GM067795 / NIGMS NIH HHS R21 AI139902 / NIAID NIH HHS R01 AI121080 / NIAID NIH HHS I01 BX002903 / BLRD VA R01 AI127481 / NIAID NIH HHS T32 AI007485 / NIAID NIH HHS T32 GM007337 / NIGMS NIH HHS R01 AI134733 / NIAID NIH HHS S10 OD016199 / NIH HHS R01 AI139874 / NIAID NIH HHS R01 AI125446 / NIAID NIH HHS P30 CA086862 / NCI NIH HHS
- Language
- English
- Date published
- 07/2020
- Academic Unit
- Molecular Physiology and Biophysics; Microbiology and Immunology; Pathology
- Record Identifier
- 9984297423802771
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