Oncotarget

Research Papers: Gerotarget (Focus on Aging):

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

Sandra Schütze _, Sandra Ribes, Annika Kaufmann, Anja Manig, Jörg Scheffel, Sandra Redlich, Stephanie Bunkowski, Uwe-Karsten Hanisch, Wolfgang Brück and Roland Nau

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Oncotarget. 2014; 5:12573-12592. https://doi.org/10.18632/oncotarget.2709

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Abstract

Sandra Schütze1,2, Sandra Ribes1, Annika Kaufmann1, Anja Manig1, Jörg Scheffel1, Sandra Redlich1, Stephanie Bunkowski1, Uwe-Karsten Hanisch1, Wolfgang Brück1, Roland Nau1,3

1Institute of Neuropathology, University Medical Center Göttingen, 37075 Göttingen, Germany

2Department of Geriatrics, Agaplesion Diakonissen Krankenhaus, 60322 Frankfurt am Main, Germany

3Department of Geriatrics, Evangelisches Krankenhaus Göttingen-Weende, 37075 Göttingen, Germany

Correspondence to:

Sandra Schütze, e-mail: sebert1@gwdg.de

Keywords: aging, bacterial CNS infection, E. coli, microglia, macrophages, phagocytosis, innate immunity

Received: October 21, 2014     Accepted: November 10, 2014     Published: November 26, 2014

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.


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