The interplay between host immunity and Clostridioides difficile infection

Clostridioides difficile infection (CDI) is a major public health concern and the leading cause of healthcare-associated infectious enteric inflammation worldwide. Disruption of the gut microbiome predisposes to C. difficile colonization, proliferation, and production of cytotoxic toxins that damage the intestinal epithelial layer. CDI treatment is challenging in part due to the emergence of antibiotic-resistant strains and the lack of efficient vaccines, predisposing individuals to recurrent CDI episodes. Consequently, there is an urgent need for the development of novel therapeutic approaches. Both innate and adaptive immune responses contribute to protection against CDI, but the cellular and molecular mechanisms underlying this process are not completely understood. In this mini review, I discuss the history and recent findings with a focus on mechanisms that drive host immunity to C. difficile, with a conclusion on where the field stands and outstanding questions that remain elusive.