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Selective expression of variant surface antigens enables Plasmodium falciparum to evade immune clearance in vivo

Author

Listed:
  • Marvin Chew

    (Nanyang Technological University
    Antimicrobial Resistance Interdisciplinary Research Group)

  • Weijian Ye

    (Nanyang Technological University
    Antimicrobial Resistance Interdisciplinary Research Group)

  • Radoslaw Igor Omelianczyk

    (Nanyang Technological University)

  • Charisse Flerida Pasaje

    (Massachusetts Institute of Technology)

  • Regina Hoo

    (Nanyang Technological University
    Wellcome Sanger Institute)

  • Qingfeng Chen

    (Agency of Science, Technology and Research)

  • Jacquin C. Niles

    (Massachusetts Institute of Technology)

  • Jianzhu Chen

    (Antimicrobial Resistance Interdisciplinary Research Group
    Massachusetts Institute of Technology)

  • Peter Preiser

    (Nanyang Technological University
    Antimicrobial Resistance Interdisciplinary Research Group)

Abstract

Plasmodium falciparum has developed extensive mechanisms to evade host immune clearance. Currently, most of our understanding is based on in vitro studies of individual parasite variant surface antigens and how this relates to the processes in vivo is not well-understood. Here, we have used a humanized mouse model to identify parasite factors important for in vivo growth. We show that upregulation of the specific PfEMP1, VAR2CSA, provides the parasite with protection from macrophage phagocytosis and clearance in the humanized mice. Furthermore, parasites adapted to thrive in the humanized mice show reduced NK cell-mediated killing through interaction with the immune inhibitory receptor, LILRB1. Taken together, these findings reveal new insights into the molecular and cellular mechanisms that the parasite utilizes to coordinate immune escape in vivo. Identification and targeting of these specific parasite variant surface antigens crucial for immune evasion provides a unique approach for therapy.

Suggested Citation

  • Marvin Chew & Weijian Ye & Radoslaw Igor Omelianczyk & Charisse Flerida Pasaje & Regina Hoo & Qingfeng Chen & Jacquin C. Niles & Jianzhu Chen & Peter Preiser, 2022. "Selective expression of variant surface antigens enables Plasmodium falciparum to evade immune clearance in vivo," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31741-2
    DOI: 10.1038/s41467-022-31741-2
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    References listed on IDEAS

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    1. Suresh M. Ganesan & Alejandra Falla & Stephen J. Goldfless & Armiyaw S. Nasamu & Jacquin C. Niles, 2016. "Synthetic RNA–protein modules integrated with native translation mechanisms to control gene expression in malaria parasites," Nature Communications, Nature, vol. 7(1), pages 1-10, April.
    2. Fumiji Saito & Kouyuki Hirayasu & Takeshi Satoh & Christian W. Wang & John Lusingu & Takao Arimori & Kyoko Shida & Nirianne Marie Q. Palacpac & Sawako Itagaki & Shiroh Iwanaga & Eizo Takashima & Takaf, 2017. "Immune evasion of Plasmodium falciparum by RIFIN via inhibitory receptors," Nature, Nature, vol. 552(7683), pages 101-105, December.
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    Cited by:

    1. Qi Zhan & Qixin He & Kathryn E. Tiedje & Karen P. Day & Mercedes Pascual, 2024. "Hyper-diverse antigenic variation and resilience to transmission-reducing intervention in falciparum malaria," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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