| Autor: |
Cremin M; Department of Anatomy, Physiology and Cell Biology, UC Davis School of Veterinary Medicine, UC Davis, Davis, California, USA., Tay E; Department of Anatomy, Physiology and Cell Biology, UC Davis School of Veterinary Medicine, UC Davis, Davis, California, USA., Ramirez VT; Department of Anatomy, Physiology and Cell Biology, UC Davis School of Veterinary Medicine, UC Davis, Davis, California, USA., Murray K; Department of Anatomy, Physiology and Cell Biology, UC Davis School of Veterinary Medicine, UC Davis, Davis, California, USA., Nichols RK; Department of Anatomy, Physiology and Cell Biology, UC Davis School of Veterinary Medicine, UC Davis, Davis, California, USA., Brust-Mascher I; Department of Anatomy, Physiology and Cell Biology, UC Davis School of Veterinary Medicine, UC Davis, Davis, California, USA., Reardon C; Department of Anatomy, Physiology and Cell Biology, UC Davis School of Veterinary Medicine, UC Davis, Davis, California, USA. |
| Abstrakt: |
Mucosal immunity is critical to host protection from enteric pathogens and must be carefully controlled to prevent immunopathology. Regulation of immune responses can occur through a diverse range of mechanisms including bi-directional communication with the neurons. Among which include specialized sensory neurons that detect noxious stimuli due to the expression of transient receptor potential vanilloid receptor 1 (TRPV1) ion channel and have a significant role in the coordination of host-protective responses to enteric bacterial pathogens. Here we have used the mouse-adapted attaching and effacing pathogen Citrobacter rodentium to assess the specific role of the TRPV1 channel in coordinating the host response. TRPV1 knockout (TRPV1 -/- ) mice had a significantly higher C. rodentium burden in the distal colon and fecal pellets compared to wild-type (WT) mice. Increased bacterial burden was correlated with significantly increased colonic crypt hyperplasia and proliferating intestinal epithelial cells in TRPV1 -/- mice compared to WT. Despite the increased C. rodentium burden and histopathology, the recruitment of colonic T cells producing IFNγ, IL-17, or IL-22 was similar between TRPV1 -/- and WT mice. In evaluating the innate immune response, we identified that colonic neutrophil recruitment in C. rodentium infected TRPV1 -/- mice was significantly reduced compared to WT mice; however, this was independent of neutrophil development and maturation within the bone marrow compartment. TRPV1 -/- mice were found to have significantly decreased expression of the neutrophil-specific chemokine Cxcl6 and the adhesion molecules Icam1 in the distal colon compared to WT mice. Corroborating these findings, a significant reduction in ICAM-1 and VCAM-1, but not MAdCAM-1 protein on the surface of colonic blood endothelial cells from C. rodentium infected TRPV1 -/- mice compared to WT was observed. These findings demonstrate the critical role of TRPV1 in regulating the host protective responses to enteric bacterial pathogens, and mucosal immune responses. |
