期刊
JOURNAL OF INFECTIOUS DISEASES
卷 217, 期 2, 页码 188-197出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jix414
关键词
aging; Clostridium difficile infection; host response; innate immunity; microbiome
资金
- National Institutes of Health/National Institute of Allergy and Infectious Diseases [U01 AI075526, T32 5T32AI007046-39]
Background. Clostridium difficile infection (CDI) is a serious threat for an aging population. Using an aged mouse model, we evaluated the effect of age and the roles of innate immunity and intestinal microbiota. Methods. Aged (18 months) and young (8 weeks) mice were infected with C difficile, and disease severity, immune response, and intestinal microbiome were compared. The same experiment was repeated with intestinal microbiota exchange between aged and young mice before infection. Results. Higher mortality was observed in aged mice with weaker neutrophilic mobilization in blood and intestinal tissue and depressed proinflammatory cytokines in early infection. Microbiota exchange improved survival and early immune response in aged mice. Microbiome analysis revealed that aged mice have significant deficiencies in Bacteroidetes phylum and, specifically, Bacteroides, Alistipes, and rc4-4 genera, which were replenished by cage switching. Conclusions. Microbiota-dependent alteration in innate immune response early on during infection may explain poor outcome in aged host with CDI.
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