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PRL2 regulates neutrophil extracellular trap formation which contributes to severe malaria and acute lung injury

Author

Listed:
  • Xinyue Du

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University School of Medicine)

  • Baiyang Ren

    (Shanghai Jiao Tong University School of Medicine
    Kunming Medical University)

  • Chang Li

    (Shanghai Jiao Tong University School of Medicine
    Kunming Medical University)

  • Qi Li

    (Shanghai Jiao Tong University School of Medicine)

  • Shuo Kan

    (Shanghai Jiao Tong University School of Medicine)

  • Xin Wang

    (Shanghai Jiao Tong University School of Medicine
    Kunming Medical University)

  • Wenjuan Bai

    (Shanghai Jiao Tong University School of Medicine)

  • Chenyun Wu

    (Shanghai Jiao Tong University School of Medicine)

  • Kokouvi Kassegne

    (Shanghai Jiao Tong University School of Medicine)

  • Huibo Yan

    (Shanghai Jiao Tong University School of Medicine)

  • Xiaoyin Niu

    (Shanghai Jiao Tong University School of Medicine)

  • Min Yan

    (Kunming Medical University)

  • Wenyue Xu

    (Army Medical University (The Third Military Medical University))

  • Samuel C. Wassmer

    (London School of Hygiene & Tropical Medicine)

  • Jing Wang

    (Shanghai Jiao Tong University School of Medicine)

  • Guangjie Chen

    (Shanghai Jiao Tong University School of Medicine)

  • Zhaojun Wang

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University School of Medicine)

Abstract

Excessive host immune responses contribute to severe malaria with high mortality. Here, we show that PRL2 in innate immune cells is highly related to experimental malaria disease progression, especially the development of murine severe malaria. In the absence of PRL2 in myeloid cells, Plasmodium berghei infection results in augmented lung injury, leading to significantly increased mortality. Intravital imaging revealed greater neutrophilic inflammation and NET formation in the lungs of PRL2 myeloid conditional knockout mice. Depletion of neutrophils prior to the onset of severe disease protected mice from NETs associated lung injury, and eliminated the difference between WT and PRL2 CKO mice. PRL2 regulates neutrophil activation and NET accumulation via the Rac-ROS pathway, thus contributing to NETs associated ALI. Hydroxychloroquine, an inhibitor of PRL2 degradation alleviates NETs associated tissue damage in vivo. Our findings suggest that PRL2 serves as an indicator of progression to severe malaria and ALI. In addition, our study indicated the importance of PRL2 in NET formation and tissue injury. It might open a promising path for adjunctive treatment of NET-associated disease.

Suggested Citation

  • Xinyue Du & Baiyang Ren & Chang Li & Qi Li & Shuo Kan & Xin Wang & Wenjuan Bai & Chenyun Wu & Kokouvi Kassegne & Huibo Yan & Xiaoyin Niu & Min Yan & Wenyue Xu & Samuel C. Wassmer & Jing Wang & Guangji, 2024. "PRL2 regulates neutrophil extracellular trap formation which contributes to severe malaria and acute lung injury," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45210-5
    DOI: 10.1038/s41467-024-45210-5
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    References listed on IDEAS

    as
    1. Prasanna Jagannathan & Abel Kakuru, 2022. "Malaria in 2022: Increasing challenges, cautious optimism," Nature Communications, Nature, vol. 13(1), pages 1-3, December.
    2. Debanjan Mukherjee & Ângelo Ferreira Chora & Jean-Christophe Lone & Ricardo S. Ramiro & Birte Blankenhaus & Karine Serre & Mário Ramirez & Isabel Gordo & Marc Veldhoen & Patrick Varga-Weisz & Maria M., 2022. "Host lung microbiota promotes malaria-associated acute respiratory distress syndrome," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
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