Can cathelicidins "activate" pathogen sensing in the gut epithelium?
Infectious inflammation of the intestine (e.g., enterocolitis incited by Salmonella enterica Typhimurium) affects humans and production animals (diarrhea is a main disease in young pigs and cattle), with concomitant zoonotic risk. Current antibiotic treatments for infectious diarrheas are not always effective and increase antibiotic resistance.
We have a series of projects, utilizing cultured colonic epithelial cells and colonoids and murine models of infectious colitis with Citrobacter rodentium (natural attaching/effacing bacterial pathogen in mice) and S. Typhimurium. We aim to define the role of cathelicidins in activating intestinal defenses to quickly resolve the inflammation of the intestine, thereby limiting disease progression and tissue destruction. We are exploring mechanisms of cathelicidins to control the production of pro-inflammatory cytokines, white blood cell trafficking, and the lining colonic mucus barrier. Our findings are further studied in models of infectious colitis in calves experimentally infected with Cryptosporidium parvum or EHEC Escherichia coli. The long-term goal is to apply this understanding of novel protective functions of cathelicidins on the development of therapeutics for controlling diarrheic enterocolitis.