title: Higher mortality and impaired elimination of bacteria in aged mice after intracerebral infection with E. coli are associated with an age-related decline of microglia and macrophage functions.
abstract: Incidence and mortality of bacterial meningitis are strongly increased in aged compared to younger adults demanding new strategies to improve prevention and therapy of bacterial central nervous system (CNS) infections the elderly. Here, we established a geriatric mouse model for an intracerebral E. coli infection which reflects the clinical situation in aged patients: After intracerebral challenge with E. coli K1, aged mice showed a higher mortality, a faster development of clinical symptoms, and a more pronounced weight loss. Elimination of bacteria and systemic inflammatory response were impaired in aged mice, however, the number of infiltrating leukocytes and microglial cells in the CNS of aged and young mice did not differ substantially. In vitro, primary microglial cells and peritoneal macrophages from aged mice phagocytosed less E. coli and released less NO and cyto-/chemokines compared to cells from young mice both without activation and after stimulation by agonists of TLR 2, 4, and 9. Our results suggest that the age-related decline of microglia and macrophage functions plays an essential role for the higher susceptibility of aged mice to intracerebral infections. Strategies to improve the phagocytic potential of aged microglial cells and macrophages appear promising for prevention and treatment of CNS infections in elderly patients.
authors.affiliation: Institute of Neuropathology, University Medical Center Göttingen, 37075 Göttingen, Germany. Department of Geriatrics, Agaplesion Diakonissen Krankenhaus, 60322 Frankfurt am Main, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Schütze
authors.affiliation: Institute of Neuropathology, University Medical Center Göttingen, 37075 Göttingen, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Ribes
authors.affiliation: Institute of Neuropathology, University Medical Center Göttingen, 37075 Göttingen, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Kaufmann
authors.affiliation: Institute of Neuropathology, University Medical Center Göttingen, 37075 Göttingen, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Manig
authors.affiliation: Institute of Neuropathology, University Medical Center Göttingen, 37075 Göttingen, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Scheffel
authors.affiliation: Institute of Neuropathology, University Medical Center Göttingen, 37075 Göttingen, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Redlich
authors.affiliation: Institute of Neuropathology, University Medical Center Göttingen, 37075 Göttingen, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Bunkowski
authors.affiliation: Institute of Neuropathology, University Medical Center Göttingen, 37075 Göttingen, Germany.
authors.forename: Uwe-Karsten
authors.initials: UK
authors.lastname: Hanisch
authors.affiliation: Institute of Neuropathology, University Medical Center Göttingen, 37075 Göttingen, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Brück
authors.affiliation: Institute of Neuropathology, University Medical Center Göttingen, 37075 Göttingen, Germany. Department of Geriatrics, Evangelisches Krankenhaus Göttingen-Weende, 37075 Göttingen, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Nau
mesh_terms: D000367:Age Factors; D000818:Animals; D001927:Brain Diseases / Q000276:immunology / Q000382:microbiology*; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000302:isolation & purification*; D004927:Escherichia coli Infections / Q000276:immunology / Q000382:microbiology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology*; D016920:Meningitis, Bacterial / Q000276:immunology / Q000382:microbiology*; D051379:Mice; D017628:Microglia / Q000276:immunology / Q000382:microbiology*