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Recombinant YopJ induces apoptotic cell death in macrophages through TLR2

Ashok Kumar Pandey1, Ajit Sodhi

  • 1Faculty of Science, School of Biotechnology, Banaras Hindu University, Varanasi 221005, India.

Molecular Immunology
|December 7, 2010
PubMed

Insights

Recombinant YopJ protein induces macrophage apoptosis via Toll-like receptor 2 (TLR2) and p38 MAP kinase signaling. Neutralizing TLR2 inhibits apoptosis, revealing a key bacterial evasion mechanism.

Area of Science:

  • Immunology
  • Microbiology
  • Cell Biology

Background:

  • Bacterial pathogens employ strategies to evade innate immune detection.
  • Toll-like receptors (TLRs) are crucial for recognizing microbial components.
  • Recombinant YopJ (rYopJ) protein has been previously shown to induce apoptosis in macrophages.

Purpose of the Study:

  • To elucidate the role of TLR2 in rYopJ-induced apoptosis in murine peritoneal macrophages.
  • To investigate the downstream signaling pathways involved in rYopJ-mediated macrophage apoptosis.

Main Methods:

  • Neutralization experiments using antibodies against TLR2.
  • Co-immunoprecipitation to assess interactions with MyD88.
  • Measurement of caspase activation (caspase-8, caspase-3).
  • Assessment of mitochondrial membrane potential (Δψm) and DNA fragmentation.
  • Analysis of protein expression (IRAK-4, FADD) and kinase phosphorylation (IκB, p38 MAP kinase).
  • Pharmacological inhibition of p38 MAP kinase.

Main Results:

  • TLR2 neutralization inhibited rYopJ-induced caspase-8, caspase-3 activation, Δψm changes, and DNA fragmentation.
  • rYopJ enhanced the expression of IRAK-4, FADD, and phosphorylation of IκB and p38 MAP kinase.
  • Inhibition of p38 MAP kinase and TLR2 neutralization significantly reduced rYopJ-induced apoptosis markers.

Conclusions:

  • TLR2 plays a critical role in mediating rYopJ-induced apoptosis in macrophages.
  • The p38 MAP kinase pathway is involved in rYopJ-induced macrophage apoptosis.
  • These findings highlight bacterial evasion mechanisms targeting innate immunity receptors like TLR2.

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