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Plasma membrane damage causes NLRP3 activation and pyroptosis during Mycobacterium tuberculosis infection

Author

Listed:
  • Kai S. Beckwith

    (Norwegian University of Science and Technology (NTNU))

  • Marianne S. Beckwith

    (Norwegian University of Science and Technology (NTNU))

  • Sindre Ullmann

    (Norwegian University of Science and Technology (NTNU))

  • Ragnhild S. Sætra

    (Norwegian University of Science and Technology (NTNU))

  • Haelin Kim

    (Norwegian University of Science and Technology (NTNU))

  • Anne Marstad

    (Norwegian University of Science and Technology (NTNU))

  • Signe E. Åsberg

    (Norwegian University of Science and Technology (NTNU))

  • Trine A. Strand

    (Norwegian University of Science and Technology (NTNU))

  • Markus Haug

    (Norwegian University of Science and Technology (NTNU))

  • Michael Niederweis

    (The University of Alabama at Birmingham)

  • Harald A. Stenmark

    (Norwegian University of Science and Technology (NTNU)
    University of Oslo, Montebello)

  • Trude H. Flo

    (Norwegian University of Science and Technology (NTNU))

Abstract

Mycobacterium tuberculosis is a global health problem in part as a result of extensive cytotoxicity caused by the infection. Here, we show how M. tuberculosis causes caspase-1/NLRP3/gasdermin D-mediated pyroptosis of human monocytes and macrophages. A type VII secretion system (ESX-1) mediated, contact-induced plasma membrane damage response occurs during phagocytosis of bacteria. Alternatively, this can occur from the cytosolic side of the plasma membrane after phagosomal rupture in infected macrophages. This damage causes K+ efflux and activation of NLRP3-dependent IL-1β release and pyroptosis, facilitating the spread of bacteria to neighbouring cells. A dynamic interplay of pyroptosis with ESCRT-mediated plasma membrane repair also occurs. This dual plasma membrane damage seems to be a common mechanism for NLRP3 activators that function through lysosomal damage.

Suggested Citation

  • Kai S. Beckwith & Marianne S. Beckwith & Sindre Ullmann & Ragnhild S. Sætra & Haelin Kim & Anne Marstad & Signe E. Åsberg & Trine A. Strand & Markus Haug & Michael Niederweis & Harald A. Stenmark & Tr, 2020. "Plasma membrane damage causes NLRP3 activation and pyroptosis during Mycobacterium tuberculosis infection," Nature Communications, Nature, vol. 11(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16143-6
    DOI: 10.1038/s41467-020-16143-6
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