No abstract

Alternatives to antibiotics for prevention of respiratory tract infections in cattle are urgently needed given the increasing public and regulatory pressure to reduce overall antibiotic usage. Activation of local innate immune defenses in the upper respiratory tract is one strategy to induce non-specific protection against infection with the diverse array of viral and bacterial pathogens associated with bovine respiratory disease complex (BRDC), while avoiding the use of antibiotics. Our prior studies in rodent models demonstrated that intranasal administration of liposome-TLR complexes (LTC) as a non-specific immune stimulant generated high levels of protection against lethal bacterial and viral pathogens. Therefore, we conducted studies to assess LTC induction of local immune responses and protective immunity to BRDC in cattle. In vitro, LTC were shown to activate peripheral blood mononuclear cells in cattle, which was associated with secretion of INFγ and IL-6. Macrophage activation with LTC triggered intracellular killing of Mannheimia hemolytica and several other bacterial pathogens. In studies in cattle, intranasal administration of LTC demonstrated dose-dependent activation of local innate immune responses in the nasopharynx, including recruitment of monocytes and prolonged upregulation (at least 2 weeks) of innate immune cytokine gene expression by nasopharyngeal mucosal cells. In a BRDC challenge study, intranasal administration of LTC prior to pathogen exposure resulted in significant reduction in both clinical signs of infection and disease-associated euthanasia rates. These findings indicate that intranasal administration of a non-specific innate immune stimulant can be an effective method of rapidly generating generalized protection from mixed viral and bacterial respiratory tract infections in cattle.

Th e objective of this study is to inventory the current genetic diversity of the bison quarantine feasibility study (BQFS) herd originating from Yellowstone National Park (YNP) using previously described microsatellite, mitochondrial and nuclear DNA markers with the aim to determine the degree, if any, of cattle DNA introgression in this herd. Th is work can provide an important tool in monitoring and managing bison genetic diversity as brucellosis-free reintroduced herds are re-established throughout the US for conservation purposes. Th e BQFS composed of 89 Bison bison from YNP that were quarantined and tested to qualify as free of brucellosis in 2006 -2007. Understanding genetic diversity of the herd is important to determine if any genetic characteristics such as cattle DNA introgression or low genetic diversity may threaten the herd ' s protected status. We evaluated genetic diversity at 42 microsatellite loci representing each of the nuclear chromosomes in the bison genome. We found no detectable evidence of cattle DNA introgression in this herd through nuclear markers and mitochondrial DNA analysis. Parentage analysis of the BQFS herd indicated that the majority of mature adults were actively breeding and contributing off spring. Genetic diversity levels in the quarantined herd were high and comparable to the YNP parent herd, suggesting a low risk of genetic loss in the near future. Based on these fi ndings, the genetic diversity currently available within the BQFS herd will provide a strong foundation for bison reintroduced herds and for the preservation of the species.

The impact of antibiotic therapy on antimicrobial drug-resistance is well known in the cattle industry yet the potential effects of antibiotic administration on immune modulation is unknown. Data from various animal models indicate that some antibiotics can suppress adaptive immune responses. Azithromycin for example, can suppress inflammation and innate immune defenses inferring that indiscriminate use of antibiotics may paradoxically increase susceptibility to infection and interfere with vaccine immunity. For cattle, we aim to identify classes of immune modulatory antibiotics to determine whether treatment interferes with vaccine responses. We hypothesize that macrolide and tetracycline antibiotics will significantly suppress immune responses in cattle which will be tested using assays that evaluate immunity in vitro.