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Inhibition of ROS and upregulation of inflammatory cytokines by FoxO3a promotes survival against Salmonella typhimurium

Author

Listed:
  • Julie Joseph

    (Faculty of Medicine, Microbiology, and Immunology, University of Ottawa)

  • Emmanuelle S. Ametepe

    (Faculty of Medicine, Microbiology, and Immunology, University of Ottawa)

  • Naveen Haribabu

    (Faculty of Medicine, Microbiology, and Immunology, University of Ottawa)

  • Gerard Agbayani

    (Faculty of Medicine, Microbiology, and Immunology, University of Ottawa
    National Research Council of Canada-Human Health Therapeutics)

  • Lakshmi Krishnan

    (Faculty of Medicine, Microbiology, and Immunology, University of Ottawa
    National Research Council of Canada-Human Health Therapeutics)

  • Alexandre Blais

    (Faculty of Medicine, Microbiology, and Immunology, University of Ottawa)

  • Subash Sad

    (Faculty of Medicine, Microbiology, and Immunology, University of Ottawa)

Abstract

Virulent intracellular pathogens, such as the Salmonella species, engage numerous virulence factors to subvert host defence mechanisms to induce a chronic infection that leads to typhoid or exacerbation of other chronic inflammatory conditions. Here we show the role of the forkhead transcription factor FoxO3a during infection of mice with Salmonella typhimurium (ST). Although FoxO3a signalling does not affect the development of CD8+ T cell responses to ST, FoxO3a has an important protective role, particularly during the chronic stage of infection, by limiting the persistence of oxidative stress. Furthermore, FoxO3a signalling regulates ERK signalling in macrophages, which results in the maintenance of a proinflammatory state. FoxO3a signalling does not affect cell proliferation or cell death. Thus, these results reveal mechanisms by which FoxO3a promotes host survival during infection with chronic, virulent intracellular bacteria.

Suggested Citation

  • Julie Joseph & Emmanuelle S. Ametepe & Naveen Haribabu & Gerard Agbayani & Lakshmi Krishnan & Alexandre Blais & Subash Sad, 2016. "Inhibition of ROS and upregulation of inflammatory cytokines by FoxO3a promotes survival against Salmonella typhimurium," Nature Communications, Nature, vol. 7(1), pages 1-14, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12748
    DOI: 10.1038/ncomms12748
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    Cited by:

    1. Qilong Li & Kunying Lv & Ning Jiang & Tong Liu & Nan Hou & Liying Yu & Yixin Yang & Anni Feng & Yiwei Zhang & Ziwei Su & Xiaoyu Sang & Ying Feng & Ran Chen & Wenyue Xu & Liwang Cui & Yaming Cao & Qiju, 2024. "SOD3 suppresses early cellular immune responses to parasite infection," Nature Communications, Nature, vol. 15(1), pages 1-10, December.

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