IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-28531-1.html
   My bibliography  Save this article

TLR4 is a regulator of trained immunity in a murine model of Duchenne muscular dystrophy

Author

Listed:
  • Salyan Bhattarai

    (Meakins-Christie Laboratories, Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre
    McGill University Health Centre)

  • Qian Li

    (Meakins-Christie Laboratories, Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre
    McGill University Health Centre)

  • Jun Ding

    (Meakins-Christie Laboratories, Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre
    McGill University Health Centre)

  • Feng Liang

    (Meakins-Christie Laboratories, Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre
    McGill University Health Centre)

  • Ekaterina Gusev

    (Meakins-Christie Laboratories, Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre
    McGill University Health Centre)

  • Orsolya Lapohos

    (Meakins-Christie Laboratories, Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre
    McGill University Health Centre)

  • Gregory J. Fonseca

    (Meakins-Christie Laboratories, Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre
    McGill University Health Centre)

  • Eva Kaufmann

    (Meakins-Christie Laboratories, Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre
    McGill University Health Centre)

  • Maziar Divangahi

    (Meakins-Christie Laboratories, Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre
    McGill University Health Centre
    McGill University)

  • Basil J. Petrof

    (Meakins-Christie Laboratories, Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre
    McGill University Health Centre)

Abstract

Dysregulation of the balance between pro-inflammatory and anti-inflammatory macrophages has a key function in the pathogenesis of Duchenne muscular dystrophy (DMD), a fatal genetic disease. We postulate that an evolutionarily ancient protective mechanism against infection, known as trained immunity, drives pathological inflammation in DMD. Here we show that bone marrow-derived macrophages from a murine model of DMD (mdx) exhibit cardinal features of trained immunity, consisting of transcriptional hyperresponsiveness associated with metabolic and epigenetic remodeling. The hyperresponsive phenotype is transmissible by bone marrow transplantation to previously healthy mice and persists for up to 11 weeks post-transplant. Mechanistically, training is induced by muscle extract in vitro. The functional and epigenetic changes in bone marrow-derived macrophages from dystrophic mice are TLR4-dependent. Adoptive transfer experiments further support the TLR4-dependence of trained macrophages homing to damaged muscles from the bone marrow. Collectively, this suggests that a TLR4-regulated, memory-like capacity of innate immunity induced at the level of the bone marrow promotes dysregulated inflammation in DMD.

Suggested Citation

  • Salyan Bhattarai & Qian Li & Jun Ding & Feng Liang & Ekaterina Gusev & Orsolya Lapohos & Gregory J. Fonseca & Eva Kaufmann & Maziar Divangahi & Basil J. Petrof, 2022. "TLR4 is a regulator of trained immunity in a murine model of Duchenne muscular dystrophy," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28531-1
    DOI: 10.1038/s41467-022-28531-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-28531-1
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-28531-1?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. Ann-Christin Wendeln & Karoline Degenhardt & Lalit Kaurani & Michael Gertig & Thomas Ulas & Gaurav Jain & Jessica Wagner & Lisa M. Häsler & Katleen Wild & Angelos Skodras & Thomas Blank & Ori Staszews, 2018. "Innate immune memory in the brain shapes neurological disease hallmarks," Nature, Nature, vol. 556(7701), pages 332-338, April.
    2. Shruti Naik & Samantha B. Larsen & Nicholas C. Gomez & Kirill Alaverdyan & Ataman Sendoel & Shaopeng Yuan & Lisa Polak & Anita Kulukian & Sophia Chai & Elaine Fuchs, 2017. "Inflammatory memory sensitizes skin epithelial stem cells to tissue damage," Nature, Nature, vol. 550(7677), pages 475-480, October.
    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. Christine Chevalier & Claudia Chica & Justine Matheau & Adrien Pain & Michael G. Connor & Melanie A. Hamon, 2024. "Epithelial cells maintain memory of prior infection with Streptococcus pneumoniae through di-methylation of histone H3," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. Moumita Datta & Stefanie M. Hansen & Ori Staszewski, 2020. "Microglial Expression of Hdac1 and Hdac2 is Dispensable for Experimental Autoimmune Encephalomyelitis (EAE) Progression," J, MDPI, vol. 3(4), pages 1-8, October.
    3. Marius Schwabenland & Omar Mossad & Annika Sievert & Adam G. Peres & Elena Ringel & Sebastian Baasch & Julia Kolter & Giulia Cascone & Nikolaos Dokalis & Andreas Vlachos & Zsolt Ruzsics & Philipp Henn, 2023. "Neonatal immune challenge poses a sex-specific risk for epigenetic microglial reprogramming and behavioral impairment," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    4. Xiaowei Bian & Minna Piipponen & Zhuang Liu & Lihua Luo & Jennifer Geara & Yongjian Chen & Traimate Sangsuwan & Monica Maselli & Candice Diaz & Connor A. Bain & Evelien Eenjes & Maria Genander & Micha, 2024. "Epigenetic memory of radiotherapy in dermal fibroblasts impairs wound repair capacity in cancer survivors," Nature Communications, Nature, vol. 15(1), pages 1-20, 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:13:y:2022:i:1:d:10.1038_s41467-022-28531-1. 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.