Adaptive immunity in the mouse model of Clostridium difficile infection (43.4)

Abstract

Clostridium difficile rivals MRSA as the most common hospital-acquired infection. C. difficile infection (CDI) can manifest as mild diarrhea to life-threatening psuedomembranous colitis. CDI occurs following a course of antibiotics, and although most patients recover fully from CDI, ~20% undergo recurrent disease caused by toxins A and/or B. Several studies demonstrate a correlation between anti-toxin antibody (Ab) and a decrease in recurrence; however; the contribution of the systemic and mucosal Ab response remains unclear. Our goal was to use the recently described mouse model of CDI to characterize the protective immune response. Mice infected with C. difficile developed protective immunity against CDI and did not develop CDI upon re-challenge. Infected mice generated both systemic and mucosal Ab directed against toxin. We infected CD4-/- mice with C. difficile, expecting they would succumb to CDI. Instead, the mice developed immunity and we found IgA anti-toxin Ab in both serum and the mucosa. pIgR-/- mice also developed serum anti-toxin Ab and were protected from CDI, indicating that mucosal anti-toxin Ab is not required for protection from CDI. Our studies suggest that protective anti-toxin Ab can be induced in T-cell deficient individuals and that systemic anti-toxin immunity may be sufficient for protection from CDI. The results should aid in development of vaccines for CDI, especially for individuals with immunodeficiency.