Virulent Mycobacterium bovis Beijing Strain Activates the NLRP7 Inflammasome in THP-1 Macrophages

PLoS One. 2016 Apr 4;11(4):e0152853. doi: 10.1371/journal.pone.0152853. eCollection 2016.

Abstract

Mycobacterium bovis is the causative agent of tuberculosis in a wide range of mammals, including humans. Macrophages are the first line of host defense. They secrete proinflammatory cytokines, such as interleukin-1 beta (IL-1β), in response to mycobacterial infection, but the underlying mechanisms by which human macrophages are activated and release IL-1β following M. bovis infection are poorly understood. Here we show that the 'nucleotide binding and oligomerization of domain-like receptor (NLR) family pyrin domain containing 7 protein' (NLRP7) inflammasome is involved in IL-1β secretion and caspase-1 activation induced by M. bovis infection in THP-1 macrophages. NLRP7 inflammasome activation promotes the induction of pyroptosis as well as the expression of tumor necrosis factor alpha (TNF-α), Chemokine (C-C motif) ligand 3 (CCL3) and IL-1β mRNAs. Thus, the NLRP7 inflammasome contributes to IL-1β secretion and induction of pyroptosis in response to M. bovis infection in THP-1 macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Caspase 1 / genetics
  • Caspase 1 / metabolism
  • Cell Line
  • Cells, Cultured
  • Chemokine CCL3 / genetics
  • Chemokine CCL3 / metabolism
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Humans
  • Inflammasomes / metabolism*
  • Interleukin-18 / genetics
  • Interleukin-18 / metabolism
  • Interleukin-1beta / biosynthesis
  • Macrophages / immunology*
  • Macrophages / metabolism*
  • Macrophages / microbiology
  • Mycobacterium bovis / immunology*
  • Mycobacterium bovis / pathogenicity
  • Pyroptosis / immunology
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Chemokine CCL3
  • Inflammasomes
  • Interleukin-18
  • Interleukin-1beta
  • NLRP7 protein, human
  • RNA, Messenger
  • RNA, Small Interfering
  • Tumor Necrosis Factor-alpha
  • Caspase 1

Grants and funding

This work was funded by MoSTRCUK international cooperation project (Project No. 2013DFG32500) http://www.istcp.org.cn, National Natural Science Foundation of China (Project No. 31572487) https://isisn.nsfc.gov.cn, Funding of State Key Lab of Agrobiotechnology (Project No. 2012SKLAB06-14) http://cbs.cau.edu.cn, 2015 CAU Foreign Experts Major Projects (Project No: 2012z018) http://cau.edu.cn, and High-end Foreign Experts Recruitment Program (Project No: GDW20151100036) http://cepms.safea.gov.cn.