title: The host immune response to Clostridium difficile.
abstract: Clostridium difficile is the most common cause of nosocomial bacterial diarrhoea in the Western world. Diarrhoea and colitis are caused by the actions of toxins A and B released by pathogenic strains of C. difficile. Adaptive immune responses to these toxins influence the outcomes of C. difficile infection (CDI). Symptomless carriers of toxinogenic C. difficile and those with a single episode of CDI without recurrence show more robust antitoxin immune responses than those with symptomatic and recurrent disease. Immune-based approaches to CDI therapy and prevention have been developed using active vaccination or passive immunotherapy targeting C. difficile toxins. Innate immune responses to C. difficile and its toxins are also central to the pathophysiology of CDI. An acute intestinal inflammatory response with prominent neutrophil infiltration and associated tissue injury is characteristic of CDI. Furthermore, inhibiting this acute inflammatory response can protect against the intestinal injury that results from exposure to C. difficile toxins in animal models. Studies examining host risk factors for CDI have led to validated clinical prediction tools for risk of primary and of recurrent disease. Risk factors associated with severe CDI with poor clinical outcomes have also been identified and include marked elevation of the peripheral white blood cell count and elevated creatinine. However, further work is needed in this area to guide the clinical application of new approaches to disease prevention and treatment including new antimicrobials as well as passive and active immunization.
authors.affiliation: Gastroenterology Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, USA.
authors.forename: Ciarán P
authors.initials: CP
authors.lastname: Kelly
authors.affiliation: Department of Medicine for the Older Person, Mater Misericordiae University Hospital and University College, Dublin, Ireland.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Kyne
mesh_terms: D056704:Adaptive Immunity; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D016360:Clostridioides difficile / Q000276:immunology*; D003015:Clostridium Infections / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D012307:Risk Factors
chemical_list: D000900:Anti-Bacterial Agents