Monoclonal anti-toxin therapy supports the protective innate immune response following <i>Clostridioides difficile</i>infection

Abstract Clostridioides difficile causes over 200,000 hospitalizations and 13,000 deaths annually in the United States. C. infects large intestine following perturbation of microbiome to cause pathology that ranges severity from diarrhea pseudomembranous colitis. Virulence factors Toxin A B are primarily drivers disease. These toxins damage epithelial barrier leading pathologic inflammation bacterial translocation. Monoclonal antibodies (mAbs) neutralize B, actoxumab bezlotoxumab, respectively, significantly reduce disease a murine model infection, however impact toxin neutralization on induction innate immune response infection is unknown. The goal this study was define quality host context anti-toxin mAb therapy. At day 2 post-infection, infected, mAb-treated mice had less despite no differences burden compared isotype-treated mice. Further, difference neutrophil infiltration or production IFNg IL-17 lymphoid cells (ILCs) observed within intestinal lamina propria infection. However, difficile-infected, increased IL-22-producing ILCs eosinophil iso-treated Both IL-22 +ILCs eosinophils promote protective findings indicate activation natural mechanisms remain intact treatment neutralizes but does not alter intestine. Merck Sharp &amp; Dohme LLC, subsidiary Co., Inc., Rahway, NJ, USA