Update on improving tick-borne disease therapy from Dr Petersen.
The overall goal of this study was to determine differences between dogs with asymptomatic versus symptomatic Lyme Disease, in order to better understand which cell types, or inflammatory factors produced by them, are helpful for controlling the disease. In this study, we identified sporting and hunting dogs at different clinical stages of Lyme Disease and sampled blood from them in the field. We have confirmed our field diagnoses with specialized assays performed by IDEXX Laboratories. In the lab, we have analyzed the percentage of Natural Killer immune cells and some markers of the activation state of these NK cells in the blood. We have found multiple interesting aspects of the canine immune response to Lyme Disease which were not previously known, and in fact will be novel contributions to the LD immunological knowledge, due to our ability to learn from asymptomatic exposed dogs which has not been done in people. We have found one subset of these cells, NKT cells, increased in dogs exposed to the bacteria that causes Lyme Disease, Borrelia burgdorferi, but do not show symptoms of Lyme Disease (asymptomatic dogs). Therefore, we hypothesize these cells are helpful in preventing Lyme Disease symptoms. The NK cells from dogs with symptomatic Lyme Disease showed a statistically enhanced inflammatory response in the presence of Lyme Disease causing bacteria, indicating that excessive inflammation may contribute to clinical disease. Additionally, a serum cytokine was elevated in asymptomatic dogs, thus this cytokine could be skewing the NK cell subset toward a less inflammatory phenotype to prevent disease. This cytokine may represent a novel therapeutic to help drive the immune response towards a healing phenotype. Finally, we have observed that NK and/or NKT cells from dogs exposed to Lyme Disease causing bacteria are able to kill target cells similar to healthy control dogs. This is further evidence that increased inflammation, and not an inability to kill bacteria, drives most of the clinical symptoms of canine Lyme Disease. Based on these results, therapies targeted towards decreasing NK cell-mediated inflammation, or to increase serum cytokines associated with NKT cell differentiation may help dogs maintain an asymptomatic state following Lyme Disease exposure. Throughout this study, we have established a good working relationship with the caretakers of the hunting and sporting dogs and have collected enough samples to meet our statistical needs for these experiments. We have prepared a strong draft of the manuscript describing our results and we plan to submit the results of these assays for publication this spring.