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NLRP3/ASC/Caspase-1 axis and serine protease activity are involved in neutrophil IL-1β processing during

Tingjuan Zhang1, Huihui Du2, Siwei Feng1

  • 1College of Animal Science and Technology, Southwest University, Chongqing, 400715, China.

Biochemical and Biophysical Research Communications
|April 16, 2019
PubMed

Insights

The NLRP3 inflammasome and neutrophil serine proteases are key to interleukin-1 beta (IL-1β) secretion by neutrophils during Streptococcus pneumoniae infections, revealing new insights into host defense mechanisms.

Area of Science:

  • Immunology
  • Microbiology
  • Cell Biology

Background:

  • Streptococcus pneumoniae causes severe diseases like pneumonia and meningitis.
  • Interleukin-1 beta (IL-1β) is crucial for host defense against S. pneumoniae.
  • IL-1β processing in neutrophils during S. pneumoniae infection is not fully understood.

Purpose of the Study:

  • To elucidate the precise mechanisms of IL-1β processing and secretion by neutrophils upon S. pneumoniae infection.
  • To identify the inflammasome pathways involved in neutrophil-mediated IL-1β secretion.

Main Methods:

  • In vitro infection of mouse peritoneal neutrophils (WT and inflammasome knockout) with S. pneumoniae.
  • Analysis of inflammasome components (NLRP3, AIM2, NLRC4) and upstream kinases (JNK).
  • Assessment of neutrophil serine proteases' role in IL-1β secretion.

Main Results:

  • NLRP3 inflammasome is essential for neutrophil IL-1β secretion; AIM2 and NLRC4 are dispensable.
  • The upstream kinase JNK regulates ASC oligomerization, caspase-1 activation, and IL-1β secretion.
  • Neutrophil serine proteases contribute to IL-1β secretion by modulating ASC oligomerization and caspase-1 activation.

Conclusions:

  • NLRP3 inflammasome-dependent and independent pathways are involved in S. pneumoniae-induced IL-1β processing in neutrophils.
  • Both the NLRP3 inflammasome pathway and neutrophil serine proteases play critical roles in IL-1β secretion.
Keywords:
IL-1βNLPR3 inflammasomeNeutrophilsSerine proteases

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