title: Toll-like Receptor function of murine macrophages, probed by cytokine induction, is biphasic and is not impaired globally with age.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago, IL 60612, United States. Electronic address: pattabiraman@uchc.edu.
authors.forename: Goutham
authors.initials: G
authors.lastname: Pattabiraman
authors.affiliation: Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago, IL 60612, United States.
authors.forename: Karol
authors.initials: K
authors.lastname: Palasiewicz
authors.affiliation: Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago, IL 60612, United States. Electronic address: duck@uic.edu.
authors.forename: David S
authors.initials: DS
authors.lastname: Ucker
mesh_terms: D000375:Aging / Q000276:immunology*; D000818:Animals; D016207:Cytokines / Q000276:immunology*; D007113:Immunity, Innate / Q000502:physiology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D051193:Toll-Like Receptors / Q000819:agonists / Q000276:immunology*
chemical_list: D016207:Cytokines; D051193:Toll-Like Receptors
keywords: Cytokines; Immunosenescence; Inflammation; Mice; Single-cell analysis