Dr. Julia Flaminio
Susceptibility to R. equi pneumonia in foals is exclusive to the first 2-3 months of life. This bacterium causes severe pneumonia, enteritis and occasionally joint infection, with significant economic losses to the horse industry, and critical concerns about equine health and well-being. R. equi is prevalent in the horse environment (soil), and foals are exposed to it immediately after birth. Importantly, R. equi survives and replicates inside immune cells (macrophages); therefore, this bacterium has developed a mechanism to escape the immune system and cause disease.
Our hypothesis is that phagocytes of the susceptible foal have impaired killing activity against R. equi because of inadequate signaling from the airway epithelial cells.
Our previous studies funded by the Harry M. Zweig Memorial Fund for Equine Research revealed that specialized phagocytes present an age-dependent limitation in their activation, which may be a consequence of inadequate stimulus. This age-dependent development of the immune system of the foal may be involved, at least in part, in the exclusive susceptibility to disease in early life. We know from studies in mice that efficient intracellular killing of R. equi is dependent on the activation of phagocytes by immune mediators (cytokines), for the generation of pathogen killing products. Cytokines can be produced by both immune cells and respiratory epithelial cells.
We would like to include in our studies the cells of the respiratory tract that encounter the bacterium in the early stages of infection. We will test the direct effect of cytokines on the immune cells for killing of R. equi. In addition, we want to learn how the epithelial cells that line the respiratory tract signal phagocytes for the presence of R. equi. The failure of these cells in the foal may lead to the progression of the infection and development of the disease. Achieving these aims will readily enhance our ability to understand this disease, such that it can be prevented and managed more effectively.