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cASCading specks

Nature Immunology volume 15, pages 698–700 (2014)Cite this article

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Inflammasome-driven inflammation extends into the extracellular space and to neighboring cells through the passive release of specks consisting of the adaptor ASC; this perpetuates the innate immune response and adds a dimension beyond interleukin 1 to autoinflammation.

The first line of host defense is the innate immune system, which has developed numerous extracellular mechanisms to combat pathogens, including complement, antimicrobial peptides and neutrophil traps. Cells of the innate immune system also have receptors that detect conserved molecular motifs associated with microbes (pathogen-associated molecular patterns) and endogenous danger signals (damage-associated molecular patterns). Several families of such pattern-recognition receptors are present both on the cell surface and in the cytoplasm, including the Toll-like receptors (TLRs), C-type lectin receptors, RIG-I-like receptors and Nod leucine-rich repeat–containing receptors (NLRs)1. Together these receptors recognize infectious particles, chemicals and crystals and damaged tissues, forming a complex system to protect the host from persistent onslaught by a multitude of agents. Two studies in this issue of Nature Immunology by Latz and colleagues2 and by Pelegrin and colleagues3 provide exciting new evidence for the unification of extracellular and intracellular inflammatory cascades that amplify the host response to danger signals.

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Figure 1: The release of ASC specks beyond macrophage borders can trigger an inflammatory cascade.

Debbie Maizels/Nature Publishing Group

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Affiliations

  1. Lori Broderick is in the Department of Pediatrics, University of California, La Jolla, San Diego, California, USA, and Rady Children's Hospital San Diego, San Diego, California, USA.

    Lori Broderick

  2. Hal M. Hoffman is in the Department of Pediatrics, the Department of Medicine, University of California, La Jolla, San Diego, California, USA, University of California, La Jolla, San Diego, California, USA, and Rady Children's Hospital San Diego, San Diego, California, USA.

    Hal M Hoffman

Authors
  1. Lori Broderick
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  2. Hal M Hoffman
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Correspondence to Hal M Hoffman.

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Competing interests

H.M.H. is a consultant for SOBI, Novartis and Regeneron.

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Broderick, L., Hoffman, H. cASCading specks. Nat Immunol 15, 698–700 (2014). https://doi.org/10.1038/ni.2942

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