Dr Laura Cook

Recurrent C. difficile infection is associated with impaired Th17 immunity to bacterial toxins rather than antibody responses, new research suggests.

In findings that may help identify and monitor patients at high risk of  recurrent C. difficile infection, Melbourne University researchers have shown that Th17 cells and interleukin 17 (Il-17) play a key role in how the immune system responds to the infection.

Dr Laura Cook and co-researchers from the University of British Columbia, Canada, noted that anti-toxin antibodies do not correlate with protection from C. difficile infection and they hypothesised that CD4+ T cell response to C. difficile toxins A and B (TcdA and TcdB) might be an alternative way to characterise pathogen-specific immunity and disease susceptibility and severity.

Published in Gastroenterology, their paper describes how they therefore analysed CD4+ T cell immunity in patients with new onset (31) versus recurrent (39) C. difficile infection and compared the results to healthy controls (21) with no clinical history of infection.

The tests showed that patients with recurrent C. difficile infection has markedly reduced levels of Th17 cells specific for the C. difficile toxin TcdB that is associated with intestinal epithelial injury, inflammation and symptoms including diarrhoea and abdominal pain.

However there was no difference in antibody responses to TcdB between groups.

The study authors said the important role of IL17 in the gut for protection against infections has been shown in previous studies, and the new work suggested that toxin-specific CD4+ T cells rather than antibodies are potentially a useful biomarker of disease severity.

“Our study highlights that Th17 cells may be a critical cell in the fight against C. difficile infection. Our assay can rapidly detect these cells in patient blood and may provide a way to monitor effectiveness of novel treatments,” said Dr Cook, a senior research officer at the Peter Doherty Institute for Infection and Immunity.