Clostridioides difficile infection (CDI) represents a significant challenge to public health. C. difficile-associated mortality and morbidity have led the U.S. CDC to designate it as an urgent threat. Moreover, recurrence or relapses can occur in up to a third of CDI patients, due in part to antibiotics being the primary treatment for CDI and the major cause of the disease. In this review, we summarize the current knowledge of innate immune responses, adaptive immune responses, and the link between innate and adaptive immune responses of the host against CDI. The other major determinants of CDI, such as C. difficile toxins, the host microbiota, and related treatments, are also described. Finally, we discuss the known therapeutic approaches and the current status of immunization strategies for CDI, which might help to bridge the knowledge gap in the generation of therapy against CDI.
Keywords: Clostridium difficile; fecal microbiota transplant; host immune response; innate lymphoid cells; microbiome; vaccine.