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Quantitative Imaging of Lineage-specific Toll-like Receptor-mediated Signaling in Monocytes and Dendritic Cells from Small Samples of Human Blood
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Effects of aging on triggering receptor expressed on myeloid cells (TREM)-1-induced PMN functions

Carl F Fortin1, Olivier Lesur, Tamas Fulop

  • 1Immunology Graduate Program, Clinical Research Center, University of Sherbrooke, 3001, 12eme Avenue Nord, Sherbrooke, Que., Canada J1H 5N4.

FEBS Letters
|March 6, 2007
PubMed

Insights

Aging impairs the function of Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) in human neutrophils. Elderly neutrophils show reduced responses to TREM-1 engagement, potentially increasing sepsis risk.

Area of Science:

  • Immunology
  • Aging Research
  • Cellular Biology

Background:

  • Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) is crucial for polymorphonuclear neutrophil (PMN) functions like phagocytosis and respiratory burst.
  • Aging is associated with increased susceptibility to infections and sepsis.

Purpose of the Study:

  • To investigate the impact of aging on TREM-1 engagement and its downstream signaling in human PMN.
  • To understand how age-related changes in TREM-1 function may contribute to increased sepsis incidence in the elderly.

Main Methods:

  • Human PMN isolated from young and elderly donors.
  • Stimulation of TREM-1 on PMN.
  • Assessment of PMN functional responses (respiratory burst, survival, degranulation).
  • Analysis of TREM-1 signaling pathways, including phosphorylation and lipid raft recruitment.

Main Results:

  • Elderly PMN exhibited impaired responses to TREM-1 engagement compared to young PMN.
  • Age-related deficits were observed in TREM-1-induced respiratory burst modulation and reversal of LPS/GM-CSF-induced PMN death.
  • Altered phosphorylation of TREM-1 signaling molecules and reduced TREM-1 recruitment to lipid rafts were noted in elderly PMN.

Conclusions:

  • Aging significantly alters TREM-1 function in human PMN, leading to diminished cellular responses.
  • Impaired TREM-1 signaling and function in the elderly may be a key factor in their higher susceptibility to sepsis.
  • These findings highlight TREM-1 as a potential therapeutic target for improving immune responses in aging populations.

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