Clostridium difficile infection is the leading cause of hospital acquired antibiotic-associated
diarrhea in the US (Bartlett, in 2006). The increased
prevalence of circulating C. difficile strains poses a significant health
threat to US health care facilities. Strains expressing the
toxin C. difficile
Transferase (CDT), in addition to Toxins A and B (TcdA and TcdB), are more virulent and are associated with higher mortality rates (Bacci et al., 2011). We recently identified a protective role for eosinophils against C. difficile
pathogenesis (Buonomo et al., 2016). We have also defined CDT's ability to increase host
inflammation and suppress protective eosinophils through a TLR2 dependent mechanism (Cowardin et al., 2016). How CDT promotes
virulence and
eosinophil suppression via TLR2 is still under investigation. We employed a
genome-wide
microarray approach to reveal divergent transcriptional profiles between protected (TLR2− / −) and unprotected (WT) mice infected with either CDT expressing or CDT
mutant strains of C. difficile. This work revealed novel host mediated TLR2-dependent
inflammatory pathways to CDT. We provide an unbiased framework for understanding the host immune response to the binary
toxin CDT produced by C. difficile and how TLR2 signaling enhances
virulence.