A single-nucleotide polymorphism in a Plasmodium berghei ApiAP2 transcription factor alters the development of host immunity

Akkaya, M. et al. (2020) A single-nucleotide polymorphism in a Plasmodium berghei ApiAP2 transcription factor alters the development of host immunity. Science Advances, 6(6), eaaw6957. (doi: 10.1126/sciadv.aaw6957) (PMID:32076635) (PMCID:PMC7002124)

Abstract

The acquisition of malaria immunity is both remarkably slow and unpredictable. At present, we know little about the malaria parasite genes that influence the host’s ability to mount a protective immune response. Here, we show that a single-nucleotide polymorphism (SNP) resulting in a single amino acid change (S to F) in an ApiAP2 transcription factor in the rodent malaria parasite Plasmodium berghei (Pb) NK65 allowed infected mice to mount a T helper cell 1 (TH1)–type immune response that controlled subsequent infections. As compared to PbNK65S, PbNK65F parasites differentially expressed 46 genes, most of which are predicted to play roles in immune evasion. PbNK65F infections resulted in an early interferon-γ response and a later expansion of germinal centers, resulting in high levels of infected red blood cell–specific TH1-type immunoglobulin G2b (IgG2b) and IgG2c antibodies. Thus, the Pb ApiAP2 transcription factor functions as a critical parasite virulence factor in malaria infections.

• Item Type: Articles
• Additional Information: Funding: This work was supported by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases. L.M.O. and M.L. were funded by NIH grant R01AI125565.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Otto, Professor Thomas and Billker, Dr Oliver
• Authors: Akkaya, M., Bansal, A., Sheehan, P. W., Pena, M., Molina-Cruz, A., Orchard, L. M., Cimperman, C. K., Qi, C.-F., Ross, P., Yazew, T., Sturdevant, D., Anzick, S. L., Thiruvengadam, G., Otto, T. D., Billker, O., Llinás, M., Miller, L. H., and Pierce, S. K.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Research Centre: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology
• Journal Name: Science Advances
• Publisher: American Association for the Advancement of Science
• ISSN: 2375-2548
• ISSN (Online): 2375-2548
• Copyright Holders: Copyright © 2020 The Authors
• First Published: First published in Science Advances 6(6):eaaw6957
• Publisher Policy: Reproduced under a Creative Commons license