کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1919167 | 1535598 | 2016 | 16 صفحه PDF | دانلود رایگان |
• Immunosenescence reflects the dysregulation of diverse immune activities.
• Macrophages have been implicated, but the role of TLR alterations is contentious.
• We find no global alterations of intrinsic macrophage TLR responsiveness with age.
• Macrophages exhibit an intriguing, aging-independent, binary response behavior.
• Widespread TLR alterations do not account for immunosenescent inflammatory status.
Aging is associated with a waning of normal immune function. This “immunosenescence” is characterized by a diverse repertoire of seemingly discreet and unbalanced immune alterations. A number of studies have suggested that aging-associated alterations in innate immune responsiveness, especially responsiveness dependent on Toll-like Receptor (TLR) engagement, are causally involved. We find, however, that the magnitude and dose-dependency of responsiveness to TLR engagement (assessed with respect to cytokine production) in distinct populations of murine macrophages are not altered generally with animal age or as a consequence of immunosenescence. Responses elicited with a wide array of TLR agonists were examined by extensive functional analyses, principally on the level of the individual cell. These studies reveal an intriguing “all-or-nothing” response behavior of macrophages, independent of animal age. Although reports to the contrary have been cited widely, aging-associated immune decline cannot be attributed to widespread alterations in the extents of TLR-dependent innate immune macrophage responses.
Journal: Mechanisms of Ageing and Development - Volume 157, July 2016, Pages 44–59