Published February 5, 2020
| Version v1
Journal article
Open
A single-nucleotide polymorphism in a Plasmodium berghei ApiAP2 transcription factor alters the development of host immunity
Creators
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Akkaya, Munir1
- Bansal, Abhisheka1
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Sheehan, Patrick W.1
- Pena, Mirna1
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Molina-Cruz, Alvaro1
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Orchard, Lindsey M.2
- Cimperman, Clare K.1
- Qi, Chen-Feng1
- Ross, Philipp3
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Yazew, Takele1
- Sturdevant, Daniel1
- Anzick, Sarah L.1
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Thiruvengadam, Girija1
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Otto, Thomas Dan4
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Billker, Oliver5
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Llinás, Manuel2
- Miller, Louis H.1
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Pierce, Susan K.1
- 1. National Institute of Allergy and Infectious Diseases
- 2. The Pennsylvania State University
- 3. University of Chicago
- 4. Wellcome Trust Sanger Institute
- 5. Umeå University
Description
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.
Data availability
All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors.Files
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Additional details
Identifiers
- DOI
- 10.1126/sciadv.aaw6957
- Other
- oai:uchicago.tind.io:11044
Funding
- National Institute of Allergy and Infectious Diseases
- intramural research grant