Effect Of Toll–Like Receptor7/8 Agonist Immunisation Of Young Crossbred Cattle On Innate Immune Stimulation Against Tick– Borne Diseases

ABSTRACT Infectious diseases of livestock are difficult to control in Africa due partly to lack of vaccines. In the absence of these vaccines, livestock production in endemic regions is constrained by the need for repeated acaricide use and/or the loss of opportunity to genetically improve the productivity of the indigenous breeds. Indigenous cattle have innate resistance to majority of diseases but are of low productivity. There is evidence that resistance to severe disease and death upon infection in indigenous breeds is linked to innate immunity and “adjuvant-only” experiments have shown that innate immunity and resistance to severe disease can be induced in susceptible higher productivity breeds. Consequently, if innate immunity can be stimulated in young calves, acute diseases and mortality can be prevented. This approach would allow genetic improvement of cattle while maintaining innate resistance. The current study tested whether single inoculation with synthetic Toll-like Receptor 7/8 (TLR7/8) agonist would trigger discernible innate immune response in F1 Friesian-Sanga crossbred cattle. The goal of this study is to stimulate the innate immune response in young cattle with the goal to mitigate disease severity and reduce mortality in crossbred animals. Our strategy is to expose the immune system of calves to TLR7/8 agonist-fortified emulsions in a water-in-oil, slow release preparation. Whether the innate immune response of crossbred calves can be stimulated by injection with synthetic toll – like receptor7/8 agonist was previously unknown. This question has been resolved by data from the current study. Three month old Friesian x Sanga (F1) calves with no evidence of prior infection were selected. Calves were conditioned for five days during which the normal rectal temperature and sizes of the pre–scapular lymph nodes were measured to establish reference dataset for cattle in the sub region. The normal rectal temperature of the Friesian x Sanga F1 cattle was 38.50C representing the first empirically determined biomarker for crossbred cattle in the West African sub region. ix Following the 5 day period of observation, the animals were randomly divided into two groups of 12 calves. One group was inoculated with the emulsion, referred to as the experimental group, but the second group was not inoculated and was referred to as the control group. Calves in the experimental group were injected, subcutaneously, with 1ml of the agonist preparation but the control cohorts (n=12) were not injected. The rectal temperature and sizes of the lymph node from individual calves were measured, at same time, (08:00 hrs) daily for additional 7 days post-inoculation. Blood samples were also collected daily for serology and genomic DNA analyses. Calves in the experimental group recorded a significant (p = 0.013) rise in the rectal temperature and sizes of the pre-scapular lymphoid organs as compared to the control calves. Also, the amount of IL-6 increased significantly (p < 0.05) from 102 to 106 pg/ml during 48 hours of injection in experimental calves. TNF–α concentration appears to increase from 100pg/ml to 1000pg/ml within 48 hours of inoculation. However the rise was not significantly different (p > 0.05) between the amount circulating in cattle from the control and experimental groups. The results from this study indicate that animals injected with the agonist have responded to stimulation and the corresponding innate responses would be expected to provide protection against multiple pathogens without the need for multiple antigen-specific vaccines. That actually is the innovation in this approach with the possibility to save cost of producing crossbred cattle in Ghana where infectious disease are widely prevalent. Success with this approach will guide development of a low-cost disease control strategy based on innate immunity stimulation that would be globally scalable for improvement of livestock productivity in the tropical and subtropical regions.