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Sterile particle-induced inflammation is mediated by macrophages releasing IL-33 through a Bruton's tyrosine

Pankaj K Mishra1,2, Mark Palma1,2, Bonnie Buechel3

  • 1Department of Medicine, Rutgers - New Jersey Medical School, Newark, NJ, USA.

Nature Materials
|January 22, 2019
PubMed

Insights

Sterile microparticles trigger a type 2 immune response via macrophage-derived interleukin-33 (IL-33), dependent on Bruton

Area of Science:

  • Immunology
  • Biomaterials Science
  • Orthopedic Surgery

Background:

  • The initiation of innate sterile inflammation from microparticle exposure, such as prosthetic wear debris, is not well understood.
  • Understanding sterile inflammation is crucial for managing complications associated with medical implants.

Purpose of the Study:

  • To elucidate the mechanisms underlying sterile inflammation induced by microparticles.
  • To identify key molecular players involved in the type 2 immune response to microparticles.
  • To explore potential therapeutic targets for periprosthetic inflammation.

Main Methods:

  • Induction of sterile inflammatory responses using microparticles in vitro and in vivo.
  • Analysis of immune cell accumulation (neutrophils, eosinophils, M2 macrophages).
  • Measurement of cytokine levels, including interleukin-33 (IL-33).
  • Investigation of signaling pathways, including caspase-1 inflammasome and Bruton's tyrosine kinase (BTK).
  • Analysis of human periprosthetic tissue samples.

Main Results:

  • Microparticle exposure induced a potent type 2 immune response characterized by neutrophil, eosinophil, and M2 macrophage accumulation.
  • Interleukin-33 (IL-33) and type 2 cytokines were elevated, independent of caspase-1 inflammasome signaling.
  • The response was critically dependent on Bruton's tyrosine kinase (BTK).
  • Macrophages produced IL-33 in a BTK-dependent manner, which was sufficient to initiate the type 2 immune response.
  • Type 2 immune responses were also observed in aseptic inflammation in patients with periprosthetic tissue.

Conclusions:

  • Microparticle-induced sterile inflammation is initiated by macrophages producing IL-33.
  • Bruton's tyrosine kinase (BTK) plays a crucial role in this process.
  • BTK and IL-33 represent potential therapeutic targets for managing wear debris-induced periprosthetic inflammation.

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