284. Age-related differences in B-cell response during Clostridioides difficile infection in mice

BACKGROUND: Clostridioides difficile (C. difficile) infection (CDI) is a leading cause of nosocomial infection that can range from mild diarrhea to life threatening pseudomembranous colitis and death. Aging as well as defects in the host immune response including failure to develop antibody response against C. difficile antigens increases the risk of bacterial colonization, hospitalization, mortality and developing recurrent CDI. The present study aimed to investigate the differences in the B cell response between young and aged C. difficile infected mice. METHODS: C57BL/6 mice were rendered susceptible to CDI via the administration of oral cefoperazone for 10 days and then the mice were challenged with 10(3) spores of C. difficile R20291 strain (Figure 1). The young (3-4 months) and aged (22-24 months) mice were euthanized at 14 days post infection (dpi). The germinal center response and IgA+ antibody-secreting cells (ASCs) were studied using multicolor flow cytometry. [Figure: see text] RESULTS: C. difficile infected aged mice exhibited greater weight loss at 4 dpi compared to young C. difficile infected mice. The gut germinal center response studied at 14 dpi showed mild changes in T follicular helper cells (CXCR5+PD-1+ of CD4+) and germinal center B cells (GL7+CD95+ of CD19+B200+) of young C. difficile infected mice, whereas the response was dampened in the aged C. difficile infected mice (Figure 2). Further, at 14 dpi ASCs (CD138+CD98+) were seen in the lamina propria of the cecum and colon of the C. difficile infected mice, but the frequencies of CD138+CD98+ ASCs as well as IgA+ ASCs were significantly lower in the C. difficile infected aged mice compare to young mice (Figure 3). [Figure: see text] [Figure: see text] CONCLUSION: The defect in B cell response during CDI may be responsible for more severe infection and recurrent CDI among aged individual compared to young individuals. It remains to be seen if age-related changes impact antibody production and whether the antibody production during primary CDI provides long-term immunity. DISCLOSURES: Vincent B. Young, MD, PhD, ASM: Senior Editor for mSphere Journal|Debiopharm: Consultant|mSphere: Senior Editor|Vendanta Biosciences: Consultant