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PubMed · 17202359

Age-associated defect in human TLR-1/2 function.

David van Duin·Subhasis Mohanty·Venetta Thomas·Sandra Ginter·Ruth R Montgomery·Erol Fikrig·Heather G Allore·Ruslan Medzhitov·Albert C Shaw
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Abstract

The effects of aging on human TLR function remain incompletely understood. We assessed TLR function and expression in peripheral blood monocytes from 159 subjects in 2 age categories, 21-30 and >65 years of age, using a multivariable mixed effect model. Using flow cytometry to assess TLR-induced cytokine production, we observed a substantial, highly significant defect in TLR1/2-induced TNF-alpha (p = 0.0003) and IL-6 (p < 0.0001) production, in older adults compared with young controls. In contrast to findings in aged mice, other TLR (including TLR2/6)-induced cytokine production appeared largely intact. These differences were highly significant even after correcting for covariates including gender, race, medications, and comorbidities. This defect in TLR1/2 signaling may result from alterations in baseline TLR1 surface expression, which was decreased by 36% in older adults (p < 0.0001), whereas TLR2 surface expression was unaffected by aging. Production of IL-6 (p < 0.0001) and TNF-alpha (p = 0.003) after stimulation by N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2R,S)-propyl]-Cys-[S]-Ser1-[S]-Lys(4) trihydrochloride was strongly associated with TLR1 surface expression. Diminished TLR1/2 signaling may contribute to the increased infection-related morbidity and mortality and the impaired vaccine responses observed in aging humans.

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AdultAgedAgingCell MembraneFemaleHumansInterleukin-6MaleMiddle AgedToll-Like Receptor 1Toll-Like Receptor 2Tumor Necrosis Factor-alphaJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't

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David van Duin, Subhasis Mohanty, Venetta Thomas, Sandra Ginter, Ruth R Montgomery, Erol Fikrig, Heather G Allore, Ruslan Medzhitov, Albert C Shaw. 2007-01-15. Age-associated defect in human TLR-1/2 function.. https://doi.org/10.4049/jimmunol.178.2.970

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