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IgM in human immunity to Plasmodium falciparum malaria

Boyle MJ 1 , Chan JA 1 , Handayuni I 2 , Reiling L 1 , Feng G 1 , Hilton A 1 Show all authors , Kurtovic L 1 , Oyong D 2 , Piera KA 2 , Barber BE 2 , William T 3 , Eisen DP 4 , Minigo G 2 , Langer C 1 , Drew DR 1 , de Labastida Rivera F 5 , Amante FH 5 , Williams TN 6 , Kinyanjui S 6 , Marsh K 6 , Doolan DL 4 , Engwerda C 5 , Fowkes FJI 1 , Grigg MJ 2 , Mueller I 7 , McCarthy JS 5 , Anstey NM 2 , Beeson JG 1

Affiliations 

  • 1 Burnet Institute for Medical Research and Public Health, Melbourne, Victoria, Australia
  • 2 Global and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia
  • 3 Infectious Diseases Society Sabah-Menzies School of Health Research Clinical Research Unit, Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia
  • 4 Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia
  • 5 QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
  • 6 Kenya Medical Research Institute (KEMRI), Centre for Geographic Medicine, Coast, KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya
  • 7 Walter and Eliza Hall Institute, Melbourne, Victoria, Australia
Sci Adv, 2019 09;5(9):eaax4489.
PMID: 31579826 DOI: 10.1126/sciadv.aax4489

Abstract

Most studies on human immunity to malaria have focused on the roles of immunoglobulin G (IgG), whereas the roles of IgM remain undefined. Analyzing multiple human cohorts to assess the dynamics of malaria-specific IgM during experimentally induced and naturally acquired malaria, we identified IgM activity against blood-stage parasites. We found that merozoite-specific IgM appears rapidly in Plasmodium falciparum infection and is prominent during malaria in children and adults with lifetime exposure, together with IgG. Unexpectedly, IgM persisted for extended periods of time; we found no difference in decay of merozoite-specific IgM over time compared to that of IgG. IgM blocked merozoite invasion of red blood cells in a complement-dependent manner. IgM was also associated with significantly reduced risk of clinical malaria in a longitudinal cohort of children. These findings suggest that merozoite-specific IgM is an important functional and long-lived antibody response targeting blood-stage malaria parasites that contributes to malaria immunity.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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