A recent article from Eric Pamer's group in Science Translational Medicine shows that Resiquimod (also known as R-848; a Toll-like receptor (TLR)-7 agonist used to treat herpes simplex virus-induced skin lesions and those caused by cutaneous T-cell lymphoma) stimulates innate antiviral responses in the intestine and restores colonization resistance against Vancomycin-resistant Enterococcus faecium (VRE).
VRE is an important cause of antibiotic-resistant infections in the hospital setting, frequently leading to sepsis. VRE thrives in the intestine of people after antibiotic treatment has depleted their indigenous microbiota, which constitutes a barrier against colonization by other pathogens (an effect known as colonization resistance). Viral infections also induce resistance against invading bacterial pathogens through poorly understood mechanisms.
This study shows that Resiquimod activates an IL-23/IL-22-dependent antiviral pathway that ultimately leads to the expression of the antimicrobial peptide Reg3γ, reestablishing colonization resistance against VRE in antibiotic-treated mice. This therefore points to a possible treatment avenue to prevent enterocccus-induced sepsis, and once again evidences the importance of transkingdom interactions in the microbial world.