865. Poor Disease Outcome from Clostridium difficile Infection in the Aged Host: Role of Impaired Innate Immunity and Altered Intestinal Microbiota in a Mouse Model
Session: Poster Abstract Session: Bacterial Infections: Pathogenesis and Immunity
Friday, October 9, 2015
Room: Poster Hall
  • ShinJH.pdf (1.9 MB)
  • Background:

    Older age is associated with worse clinical outcomes as well as higher incidence of Clostridium difficile infection (CDI). Effects of aging have been attributed to factors such as waning immune response and alteration in intestinal microbiome. Our goal is to model CDI in the elderly in a mouse model and to investigate potential mechanisms leading to worse outcome.


    Young (8 weeks old) and aged (18 months old) mice were infected with VPI 10463 after broad spectrum antibiotic exposure. Mice were monitored for mortality, weight loss, and signs of disease. A group of mice was euthanized on days 2 and 5 to harvest blood and intestinal tissue for immune cell counts and cytokine measurement. In another experiment, dirty cage bottoms containing mouse feces were switched every other day between young and aged mice for one week prior to antibiotic exposure and infection. Changes in outcomes, cellular immune responses, and cytokine responses were measured post-cage switching.


    Clinical outcome was significantly worse in aged mice compared to young mice, with higher mortality, more diarrhea and delayed but persistent weight loss. Measures of innate immune response, such as peripheral blood and cecal neutrophil counts and levels of pro-inflammatory cytokines in cecal tissue, were significantly lower in aged mice compared to young mice at day 2 post-infection, but not at day 5.Microbiota analysis showed lower number of Bacteroidetes in the stool of the aged mice before antibiotics, which disappeared after switching of the cage bottoms. With cage switching, the mortality in the aged mice improved significantly but diarrhea and weight loss were still worse. The immune response differences on day 2 between aged and young mice became no longer apparent with cage switching.


    Using the aged mouse model of CDI, we were able to demonstrate significantly worse clinical outcome in the aged host, associated with impaired innate immune response. The effects of aging were substantially prevented by cage switching, indicating pronounced influence of the interaction between intestinal microbiota and innate immune response on disease outcome.

    Jae Hyun Shin, MD, John Moore II, MS, David Bolick, MS, Glynis Kolling, PhD and Cirle Warren, MD, Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA


    J. H. Shin, None

    J. Moore II, None

    D. Bolick, None

    G. Kolling, None

    C. Warren, None

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