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Sensors of the innate immune system: their mode of action

Nature Reviews Rheumatology volume 5, pages 448–456 (2009)Cite this article

Abstract

The discovery of molecular sensors that enable eukaryotes to recognize microbial pathogens and their products has been a key advance in our understanding of innate immunity. A tripartite sensing apparatus has developed to detect danger signals from infectious agents and damaged tissues, resulting in an immediate but short-lived defense response. This apparatus includes Toll-like receptors, retinoid acid-inducible gene-I-like receptors and other cytosolic nucleic acid sensors, and nucleotide-binding and oligomerization domain-like receptors; adaptors, kinases and other signaling molecules are required to elicit effective responses. Although this sensing is beneficial to the host, excessive activation and/or engagement by self molecules might induce autoimmune and other inflammatory disorders.

Key Points

  • Eukaryotes have evolved a cellular innate immune system, comprising three sets of cellular sensors, to detect and eradicate microbes; this system is nonspecific and rapid in its response

  • Toll-like receptors are present on cell surfaces and endosomal compartments, whereas retinoid acid-inducible gene-I-like receptors and nucleotide-binding and oligomerization domain-like receptors are present in the cytosol; although they evolved to discriminate foreign from self, these sensors can also recognize products derived from stressed or damaged cells

  • Engagement of the innate sensors initiates signaling pathways that result in the production of proinflammatory cytokines and other molecules that promote elimination of the offending agent; however, autoimmune or autoinflammatory diseases might develop if these pathways are overstimulated or uncontrolled

  • Understanding the innate immune sensors, their specificity and their signaling pathways provides the basis for new emerging concepts regarding the pathogenesis and treatment of a wide spectrum of rheumatic diseases

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Figure 1: TLR-mediated signaling.
Figure 2: RLR-mediated signaling.
Figure 3: Signaling by NOD1 and NOD2.
Figure 4: Inflammasome activation.

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Acknowledgements

The work of the authors is supported by NIH grants. Space limitations precluded citation of many original publications, and we apologize for these omissions.

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Authors and Affiliations

  1. Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA

    Roberto Baccala, Rosana Gonzalez-Quintial, Brian R. Lawson, Dwight H. Kono & Argyrios N. Theofilopoulos

  2. Department of Genetics, The Scripps Research Institute, La Jolla, CA, USA

    Bruce Beutler

  3. Allergan, Irvine, CA, USA

    Michael E. Stern

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Baccala, R., Gonzalez-Quintial, R., Lawson, B. et al. Sensors of the innate immune system: their mode of action. Nat Rev Rheumatol 5, 448–456 (2009). https://doi.org/10.1038/nrrheum.2009.136

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