Modulation of immune responses to Clostridium difficile by peroxisome proliferator-activated receptor γ and miRNA-146b

Viladomiu, M., R. Hontecillas, M. Pedragosa, P. Michalak, K. Michalak, R.L. Guerrant, J.K. Roche, C.A. Warren and J. Bassaganya-Riera (2012) Modulation of immune responses to Clostridium difficile by peroxisome proliferator-activated receptor γ and miRNA-146b, American Association of Immunologists Annual Meeting, Boston MA

Clostridium difficile is typically a harmless anaerobic bacterium but has recently re- emerged as a pathogen that can cause nosocomial diarrhea, colitis and death. It grows in the intestine of individuals whose microflora has been altered. Many countries have reported an increase in incidence of C. difficile-associated disease (CDAD) over the last years. Current treatments for CDAD do not restore the normal microflora and have not been effective in clostridial clearance, but further prolong C. difficile shedding. Hence, the discovery of novel therapeutic approaches that effectively control CDAD is important. Conclusions: 1) C. difficile increases miRNA-146b expression, which blocks NCOA4, thus reducing PPAR γ activation; 2) The loss of PPAR γ in T cells worsens CDAD; 3) Computational modeling approaches can predict novel molecular target and therapeutics 4) Oral administration of PPAR γ agonists represents a novel broad-based host targeted therapeutic for CDAD.