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.
Highlights
One major health issue arising with age is the increasing prevalence and severity of infectious diseases [1, 2]
Clinical studies demonstrated that both the incidence and mortality of community- and hospital-acquired bacterial meningitis caused by different pathogens are strongly elevated in persons > 60 years compared to younger adults [5, 9, 6]
We established a geriatric mouse model for an intracerebral E. coli infection which reflects the clinical situation in aged patients with central nervous system (CNS) infections: Aged mice showed a higher mortality (73%) than young mice (47%) after intracerebral injection of E. coli K1
Summary
One major health issue arising with age is the increasing prevalence and severity of infectious diseases [1, 2]. In healthy aging the expression of TLR on the surface of phagocytes appears not to decrease [27, 28, 29, 30] At present, it is unknown, whether microglia in old age behave in the same way as macrophages and lose their ability to phagocytose and kill pathogens or whether their function is unaffected by age. It is unknown, whether microglia in old age behave in the same way as macrophages and lose their ability to phagocytose and kill pathogens or whether their function is unaffected by age For these reasons, in the present study, we compared the ability of young and aged microglial cells to phagocytose and kill bacteria as well as the course of E. coli meningitis induced by inoculation of bacteria into the CNS in young and healthy aged mice
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