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Immunology

Organelle stress triggers inflammation

Nature volume 532, pages 321–322 (2016)Cite this article

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The intracellular NOD1 and NOD2 receptors have been found to activate innate inflammation when a condition known as endoplasmic reticulum stress is induced by bacterial infection. See Letter p.394

The ability of mammalian cells to recognize and respond to pathogenic invaders at the earliest stages of infection is crucial for immunity. Many host-cell receptors have been identified that recognize evolutionarily conserved microbial components, such as cell-wall peptidoglycan, to rapidly activate the innate immune system1. In this issue, Keestra-Gounder et al.2 (page 394) describe a curious connection whereby stress in the endoplasmic reticulum (ER), a membrane-bound compartment responsible for the synthesis of secreted cytokine proteins, triggers a cytoplasmic 'danger' signal leading to the release of inflammatory proteins that activate an innate immune response. Even more surprisingly, this ER stress signal is transduced through NOD1 and NOD2 — sensors that respond to fragments of bacterial peptidoglycans — yet takes place in the absence of these molecules.

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Figure 1: NOD proteins respond to infection through distinct pathways.

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Authors and Affiliations

  1. Bennett H. Penn is in the Department of Medicine, Division of Infectious Diseases, University of California, San Francisco, San Francisco, California 94143, USA.,

    Bennett H. Penn

  2. Jeffery S. Cox is in the Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720-3370, USA.,

    Jeffery S. Cox

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  1. Bennett H. Penn
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  2. Jeffery S. Cox
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Correspondence to Bennett H. Penn or Jeffery S. Cox.

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Penn, B., Cox, J. Organelle stress triggers inflammation. Nature 532, 321–322 (2016). https://doi.org/10.1038/nature17882

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