Hailey Barker
University of Florida
Co-Author: Mariola J. Ferraro (Edelmann)1
1University of Florida
Due to the rise of multi-drug resistant strains of disease-causing microbes from the overuse of treatments such as antibiotics, there is a need for a shift toward alternative therapies which target the host immune system. With the prevalence of drug-resistant strains of enteric pathogens, foodborne illnesses such as Salmonella Typhimurium are becoming harder to treat with traditional antibiotics. Salmonella Typhimurium is a Gram-negative intracellular bacterium that relies on the ability to infect a variety of cells, including antigen-presenting cells such as macrophages, to cause an infection. The endocannabinoid (eCB) system is a pathway composed of bioactive lipids called endocannabinoids (eCBs, a set of receptors and associated biosynthesis/degradative proteins. The cannabinoid receptors type 1 and 2 (CB1R and CB2R) are coupled to G-proteins widely expressed among many cell types. CB2R is highly expressed in immune cells and may play a role in cell proliferation and differentiation. However, there is a lack of understanding of how cannabinoid receptors (CB1R and CB2R) participate in downstream signaling functions in immune cells during bacterial infections. By further understanding the role of cannabinoid receptors in bacterial infections, cannabinoid receptors could provide for a novel target for therapies against Salmonella. Our study aimed to characterize the role of cannabinoid receptors 1 and 2 (CB1R and CB2R) in activating the immune system and preventing the colonization of Salmonella. To study this, we challenged wild-type, CB1R knockout, and CB2R knockout mice with Salmonella Typhimurium. Four days post-infection, an array of experimentations was performed to evaluate the burden of infection, proinflammatory response, and polarization of macrophages. Mice lacking the CB1R or CB2R showed increased colonization of Salmonella in the liver and spleen as well as increased inflammatory responses. Post-infection, macrophages lacking CB1R and CB2R primarily polarized towards an M1 phenotype characterized by increased pro-inflammatory response compared to macrophages derived from wild-type mice. Overall, our results indicate the potential role of CB1R and CB2R to play a protective role in vivo against Salmonella infection. Future directions will include using select cannabinoids as treatments for mice challenged against Salmonella.