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An NLRP7-containing inflammasome mediates recognition of microbial lipopeptides in human macrophages

Sonal Khare1, Andrea Dorfleutner, Nicole B Bryan

  • 1Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

Immunity
|February 25, 2012
PubMed

Insights

Researchers identified a new NLRP7 inflammasome in human macrophages. This inflammasome responds to microbial lipopeptides, activating caspase-1 to mature inflammatory cytokines and restrict bacterial growth.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Pattern recognition receptors (NLRs) sense danger signals, initiating inflammasome assembly and cytokine release.
  • The specific roles and agonists for most NLRs in innate immunity remain largely unknown.

Purpose of the Study:

  • To identify and characterize novel inflammasomes involved in innate immunity.
  • To elucidate the function of the NLRP7 inflammasome in human macrophages.

Main Methods:

  • Identification and characterization of NLRP7 inflammasome in human macrophages.
  • Stimulation with microbial acylated lipopeptides.
  • Assays for caspase-1 activation, cytokine maturation (IL-1β, IL-18), and bacterial replication.

Main Results:

  • NLRP7 inflammasome activation was induced by microbial acylated lipopeptides.
  • NLRP7 promoted ASC-dependent caspase-1 activation and maturation of IL-1β and IL-18.
  • NLRP7 activation restricted intracellular bacterial replication but did not affect IL-6 or TNF-α secretion.

Conclusions:

  • NLRP7 is a key inflammasome in human macrophages activated by microbial components.
  • NLRP7 plays a role in host defense through caspase-1-dependent cytokine maturation and bacterial restriction.

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