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Innate Immune Function by Toll-like Receptors: Distinct Responses in Newborns and the Elderly

Journal

IMMUNITY
Volume 37, Issue 5, Pages 771-783

Publisher

CELL PRESS
DOI: 10.1016/j.immuni.2012.10.014

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Funding

  1. Career Award in the Biomedical Sciences from the Burroughs Wellcome Fund
  2. Michael Smith Foundation for Health Research Career Investigator Award
  3. GlaxoSmithKline
  4. Advaxis
  5. U.S. National Institutes of Health (NIH) [RO1 AI067353-01A1]
  6. American Recovery and Reinvestment Act Administrative Supplement [3R01AI067353-05S1]
  7. Global Health Grant from The Bill & Melinda Gates Foundation [OPPGH5284]
  8. VentiRx Pharmaceuticals
  9. NIH [HHSN272201100019C, U19 AI 089992]
  10. government of the Walloon Region
  11. GlaxoSmithKline Biologicals

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Given the inborn nature of the innate immune system, it is surprising to find that innate immune function does in fact change with age. Similar patterns of distinct Toll-like-receptor-mediated immune responses come to light when one contrasts innate immune development at the beginning of life with that toward the end of life. Importantly, these developmental patterns of innate cytokine responses correlate with clinical patterns of susceptibility to disease: A heightened risk of suffering from excessive inflammation is often detected in prematurely born infants, disappears over the first few months of life, and reappears toward the end of life. In addition, risk periods for particular infections in early life reemerge in older adults. The near-mirror-image patterns that emerge in contrasts of early versus late innate immune ontogeny emphasize changes in host-environment interactions as the underlying molecular and teleologic drivers.

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