Innate immune responses in bovine forestomachs are mediated by toll like receptors

Interleukin-1/Toll Like Receptors (IL-1R/TLRs) play an important role in the inflammatory responses under a tightl regulation. TIR8, also known as SIGIRR (Single Immunoglobulin IL-1R-Related molecule), is an orphan receptor belonging to the IL-1R/TLRs super-family, playing an important role in modulating the inflammatory response in the gastrointestinal tract in mice as an interleukin-1 (IL-1) receptor family antagonist. Previous studies demonstrated the active role of bovine forestomachs as key player in immune responses during alimentary disorders and inflammatory and infective processes in both the gastrointestinal (GI) tract and elsewhere. We demonstrated the potential of bovine forestomachs to receive, elaborate and produce signals and mediators of the innate immune response. In this respect, we showed the expression of TIR8, TLR4, IL-1, IL-10 and Caspase-1 in the forestomach wall, both by Real-Time PCR and Western blot. Furthermore, we demonstrated for the first time the presence of leukocytes and immune mediators, such as interferon gamma (IFN), in the rumen liquor. In particular, CD45-positive cells (by FACS and Real-Time PCR analysis) were demonstrated in the rumen content of fistulated cows. We also recovered from the ruminal content IFN that showed a moderate stability. Newly synthesized IFN was also identified in the ruminal content after fermentation. All these points of evidence suggest an active role of the forestomachs in the immune modulation of the GI tract, but also during inflammatory disorders in other body compartments, such as uterus and joints. Forestomachs can receive signals and elaborate them, but can also send signals to the immune cells infiltrating the rumen content or other body compartments. Forestomachs have thus the capability to participate in a cross-talk with the immune system at both regional and systemic levels.