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Defective TLR‐2‐Dependent Induction of IL‐6 by Macrophages in Aged Humans
Author(s) -
Nguyen Joseph Tri,
Gollapudi Sastry,
Agrawal Sudhanshu,
Gupta Sudhir
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.672.31
Subject(s) - cd14 , cd16 , immunology , monocyte , inflammation , innate immune system , biology , peripheral blood mononuclear cell , immune system , tumor necrosis factor alpha , flow cytometry , macrophage , cd8 , cd3 , in vitro , biochemistry
Aging represents a state of paradoxical chronic inflammation and immune deficiency. However, a role of monocytes in inflammation associated with aging has not been studied in detail. Recent evidence suggests that monocytes are heterogeneous with regards to phenotype and functions. In this study, we have compared the phenotypically heterogeneous monocytes for their innate immune functions in elderly subjects. Whole peripheral blood mononuclear cells were stimulated with Pam‐3Cys (TLR‐2 agonist) and LPS (TLR‐4 agonist). Monocytes were surface stained with anti‐CD14 and anti‐CD16 antibodies, and isotype controls, then permeabilized and stained for intracellular cytokines IL‐6 and TNFalpha. Production of cytokines and TLR‐2 and TLR‐4 expression were analyzed in four subsets of monocytes (CD14+CD16+; CD14++CD16+; CD14+CD16−; CD14++CD16−) by multicolor flow cytometry. The proportion of all four subsets of monocytes as well as expression of TLR‐2 and TLR‐4 were comparable in young and aged subjects. LPS‐induced IL‐6 and TNFa producing monocytes were also comparable. However, Pam‐3cys‐induced IL‐6 production by all four monocyte subsets was significantly decreased in aged humans. This would suggest a defect in signaling downstream of TLR‐2 in monocyte subset in aged humans, which is currently being investigated.