Eosinophils may be unexpected heroes in the battle against Clostridium difficile infection

By Liz Meszaros, MDLinx
Published July 5, 2016

Key Takeaways

Eosinophils have been linked—for over 100 years—to conditions including asthma, atopic dermatitis, and allergic rhinitis. Recently, however, researchers found that eosinophils may also have a protective role in battling Clostridium difficile infection (CDI), specifically via the cytokine IL-25, which seems to have a protective effect against CDI via the manufacture of eosinophils that protect the integrity of the lining of the gut. Their results are published online in the journal Cell Reports.

“We found that if you deplete eosinophils, either genetically or by an antibody neutralization, you lost the integrity of the epithelial barrier in the gut,” said lead researcher Erica L. Buonomo, PhD, of the Department of Microbiology, Immunology and Cancer, at the University of Virginia Charlottesville, VA.

“Maintaining that barrier is very important for having a healthy response to C. difficile. It also prevents bacteria from spreading to other sites in the body, so if you have a breakdown in the barrier, you can have a septic response or bacteria in your blood or in other systemic organs,” she added.

In this study, Dr. Buonomo and colleagues evaluated the protein regulation of IL-25 in human CDI by staining colon biopsies from both CDI-negative and CDI-positive patients, which they scored for IL-25 staining. In CDI patients, they observed significant reductions in IL-25 expression compared with controls.

They also assessed reductions in IL-25 expression caused by antibiotic treatments by measuring IL-25 protein in the cecum of mice left untreated, those given only antibiotics, or on days 1, 2, and 3 after CDI. After analysis via immunohistochemical staining of the cecum and of total protein in cecal lysates, they found that IL-25 expression was not only suppressed by antibiotics, but further diminished on day 3 of CDI, suggesting that the CDI environment sustains and further decreases IL-25 protein levels compared with antibiotic treatment.

In addition, they found that once IL-25 levels were restored, disease severity decreased equivalent levels of C. difficile and toxins in the gut lumen, and that IL-25 treatment reduced mortality and morbidity and enhanced integrity of gut epithelial barrier in an eosinophil-dependent manner. Finally, upon depletion of eosinophils, Dr. Buonomo and colleagues found an increase in intestinal eosinophils and a loss of IL-25 protection, showing that gut eosinophils mediated IL-25 protection.

“We found that if you deplete eosinophils, either genetically or by an antibody neutralization, you lost the integrity of the epithelial barrier in the gut. Maintaining that barrier is very important for having a healthy response to C. difficile. It also prevents bacteria from spreading to other sites in the body, so if you have a breakdown in the barrier, you can have a septic response or bacteria in your blood or in other systemic organs,” concluded Dr. Buonomo.

This study was funded by the National Institutes of Health, grants R01AI026649-25, 1R01AI124214, R21AI114734, T32AI07496, F31AI114203 and T32AI07046-38.

Share with emailShare to FacebookShare to LinkedInShare to Twitter
ADVERTISEMENT