4.7 Review

Constitutive immune mechanisms: mediators of host defence and immune regulation

Journal

NATURE REVIEWS IMMUNOLOGY
Volume 21, Issue 3, Pages 137-150

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41577-020-0391-5

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Funding

  1. European Research Council (ERC-AdG ENVISION) [786602]
  2. Novo Nordisk Foundation [NNF18OC0030274]
  3. Lundbeck Foundation [R1982015-171, R268-2016-3927]
  4. European Research Council (ERC-StG IDEM) [637647]
  5. Howard Hughes Medical Institute-Wellcome International Research Scholarship
  6. Sylvia and Charles Viertel Foundation
  7. Aarhus University Research Foundation [AUFF-E-215-FLS-8-66]
  8. Danish Council for Independent Research-Medical Sciences [4004-00047B]
  9. European Research Council (ERC) [637647, 786602] Funding Source: European Research Council (ERC)

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This review compares and contrasts the inducible and constitutive mechanisms of immunosurveillance, showing the effectiveness and potential risks of immune responses, as well as the importance of maintaining homeostasis through a variety of immune mechanisms.
The immune system enables organisms to combat infections and to eliminate endogenous challenges. Immune responses can be evoked through diverse inducible pathways. However, various constitutive mechanisms are also required for immunocompetence. The inducible responses of pattern recognition receptors of the innate immune system and antigen-specific receptors of the adaptive immune system are highly effective, but they also have the potential to cause extensive immunopathology and tissue damage, as seen in many infectious and autoinflammatory diseases. By contrast, constitutive innate immune mechanisms, including restriction factors, basal autophagy and proteasomal degradation, tend to limit immune responses, with loss-of-function mutations in these pathways leading to inflammation. Although they function through a broad and heterogeneous set of mechanisms, the constitutive immune responses all function as early barriers to infection and aim to minimize any disruption of homeostasis. Supported by recent human and mouse data, in this Review we compare and contrast the inducible and constitutive mechanisms of immunosurveillance.

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