IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-44687-4.html
   My bibliography  Save this article

Disparate macrophage responses are linked to infection outcome of Hantan virus in humans or rodents

Author

Listed:
  • Hongwei Ma

    (Air Force Medical University (the Fourth Military Medical University)
    Air Force Medical University (the Fourth Military Medical University))

  • Yongheng Yang

    (Air Force Medical University (the Fourth Military Medical University))

  • Tiejian Nie

    (Air Force Medical University (the Fourth Military Medical University))

  • Rong Yan

    (Air Force Medical University (the Fourth Military Medical University))

  • Yue Si

    (Air Force Medical University (the Fourth Military Medical University))

  • Jing Wei

    (Air Force Medical University (the Fourth Military Medical University)
    Shaanxi Provincial Centre for Disease Control and Prevention)

  • Mengyun Li

    (Air Force Medical University (the Fourth Military Medical University))

  • He Liu

    (Air Force Medical University (the Fourth Military Medical University))

  • Wei Ye

    (Air Force Medical University (the Fourth Military Medical University))

  • Hui Zhang

    (Air Force Medical University (the Fourth Military Medical University))

  • Linfeng Cheng

    (Air Force Medical University (the Fourth Military Medical University))

  • Liang Zhang

    (Air Force Medical University (the Fourth Military Medical University))

  • Xin Lv

    (Air Force Medical University (the Fourth Military Medical University))

  • Limin Luo

    (Air Force Hospital of Southern Theatre Command)

  • Zhikai Xu

    (Air Force Medical University (the Fourth Military Medical University))

  • Xijing Zhang

    (Air Force Medical University (the Fourth Military Medical University))

  • Yingfeng Lei

    (Air Force Medical University (the Fourth Military Medical University))

  • Fanglin Zhang

    (Air Force Medical University (the Fourth Military Medical University))

Abstract

Hantaan virus (HTNV) is asymptomatically carried by rodents, yet causes lethal hemorrhagic fever with renal syndrome in humans, the underlying mechanisms of which remain to be elucidated. Here, we show that differential macrophage responses may determine disparate infection outcomes. In mice, late-phase inactivation of inflammatory macrophage prevents cytokine storm syndrome that usually occurs in HTNV-infected patients. This is attained by elaborate crosstalk between Notch and NF-κB pathways. Mechanistically, Notch receptors activated by HTNV enhance NF-κB signaling by recruiting IKKβ and p65, promoting inflammatory macrophage polarization in both species. However, in mice rather than humans, Notch-mediated inflammation is timely restrained by a series of murine-specific long noncoding RNAs transcribed by the Notch pathway in a negative feedback manner. Among them, the lnc-ip65 detaches p65 from the Notch receptor and inhibits p65 phosphorylation, rewiring macrophages from the pro-inflammation to the pro-resolution phenotype. Genetic ablation of lnc-ip65 leads to destructive HTNV infection in mice. Thus, our findings reveal an immune-braking function of murine noncoding RNAs, offering a special therapeutic strategy for HTNV infection.

Suggested Citation

  • Hongwei Ma & Yongheng Yang & Tiejian Nie & Rong Yan & Yue Si & Jing Wei & Mengyun Li & He Liu & Wei Ye & Hui Zhang & Linfeng Cheng & Liang Zhang & Xin Lv & Limin Luo & Zhikai Xu & Xijing Zhang & Yingf, 2024. "Disparate macrophage responses are linked to infection outcome of Hantan virus in humans or rodents," Nature Communications, Nature, vol. 15(1), pages 1-25, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-44687-4
    DOI: 10.1038/s41467-024-44687-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-44687-4
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-44687-4?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Enyong Dai & Leng Han & Jiao Liu & Yangchun Xie & Herbert J. Zeh & Rui Kang & Lulu Bai & Daolin Tang, 2020. "Ferroptotic damage promotes pancreatic tumorigenesis through a TMEM173/STING-dependent DNA sensor pathway," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Zhi Lin & Jiao Liu & Fei Long & Rui Kang & Guido Kroemer & Daolin Tang & Minghua Yang, 2022. "The lipid flippase SLC47A1 blocks metabolic vulnerability to ferroptosis," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-44687-4. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.