Age-associated defects in the adaptive immune response to Clostridium difficile infection impair the development of a protective immune response in the elderly

Abstract

Abstract Clostridium difficile is the number one cause of healthcare-associated infection in the United States and the most lethal acute enteric pathogen. The elderly (≥65) have the greatest risk of C. difficile infection (CDI) and severe morbidity and mortality due to CDI. Additionally, most recurrent CDIs occur within the elderly. To better understand why the elderly are at greater risk of severe and recurrent CDI, our lab has conducted a longitudinal study of the aging immune response to primary and recurrent CDI in patients at Hahnemann University Hospital. Both elderly and young CDI patients were enrolled in the study, and stool and blood samples were collected at enrollment and 12 days after diagnosis of CDI. Analysis of the samples looking at the humoral response in elderly versus young CDI patients shows that the early humoral response in elderly patients is impaired when compared to young CDI patients. In addition, recurrent CDI patients have similarly defective humoral responses. Finally, preliminary work in an aging mouse model of CDI further supports that age-related defects within the adaptive immune response impair the development of a protective immune response. Since the adaptive immune response to CDI plays an important role in neutralizing toxins produced by C. difficile, an impaired humoral response in both aged and recurrent CDI patients may contribute to the increased risk of infection, morbidity, and mortality observed in elderly patients. Future studies will seek to further characterize the aging immune response using patient samples as well as aging mouse models of CDI.