Elsevier

Anaerobe

Volume 53, October 2018, Pages 56-63
Anaerobe

Clostridioides (Clostridium) difficile (including epidemiology)
Neutralization of macrophage migration inhibitory factor improves host survival after Clostridium difficile infection

https://doi.org/10.1016/j.anaerobe.2018.06.014Get rights and content
Under a Creative Commons license
open access

Highlights

  • Systemic MIF level is high in C. difficile infected patients and mice.

  • Neutralizing MIF may improve disease severity and survival in mice infected with C. difficile.

  • Presence of MIF does not affect the pathogen burden but aggravates the degree of colonic inflammation in CDI.

Abstract

Clostridium difficile is an important cause of nosocomial diarrhea in the western world. Toxins (A, B, and binary toxins) generated by C. difficile bacteria damage intestinal epithelial cells. Hallmarks of host response to C. difficile infection (CDI) include upregulation of inflammatory mediators and tissue infiltration by immune cells. Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine that is known to enhance the host immune response to infectious pathogens. Additionally, MIF can adversely impact host survival to numerous infections. The role of MIF in the pathogenesis of CDI remains poorly understood. Here, we show that patients with CDI had significantly higher circulating MIF compared to patients who had diarrhea but tested negative for C. difficile (non-CDI controls). Similarly, in a mouse model, C. difficile challenge significantly increased levels of plasma and tissue MIF. Antibody-mediated depletion of MIF decreased C. difficile-induced inflammatory responses, clinical disease, and mortality. Together, these results uncover a potential role for MIF in exacerbating CDI and suggest that use of anti-MIF antibodies may represent a therapeutic strategy to curb host inflammatory responses and improve disease outcomes in CDI.

Cited by (0)