Search

Bovine tuberculosis (bTB), caused by infection with Mycobacterium bovis, continues to be a major economic burden associated with production losses and a public health concern due to its zoonotic nature. As with other intracellular pathogens, cell-mediated immunity plays an important role in the control of infection. Characterization of such responses is important for understanding the immune status of the host, and to identify mechanisms of protective immunity or immunopathology. This type of information can be important in the development of vaccination strategies, diagnostic assays, and in predicting protection or disease progression. However, the frequency of circulating M. bovis-specific T cells are often low, making the analysis of such responses difficult. As previously demonstrated in a different cattle infection model, antigenic expansion allows us to increase the frequency of antigen-specific T cells. Moreover, the concurrent assessment of cytokine production and proliferation provides a deeper understanding of the functional nature of these cells. The work presented here, analyzes the T cell response following experimental M. bovis infection in cattle via in vitro antigenic expansion and re-stimulation to characterize antigen-specific CD4, CD8, and γδ T cells and their functional phenotype, shedding light on the variable functional ability of these cells. Data gathered from these studies can help us better understand the cellular response to M. bovis infection and develop improved vaccines and diagnostic tools.

Mycobacterium bovis is the cause of tuberculosis in most animals, most notably cattle. The stereotypical lesion of bovine tuberculosis is the granuloma; a distinct morphological lesion where host and pathogen interact and disease outcome (i.e., dissemination, confinement, or resolution) is determined. Accordingly, it is critical to understand host-pathogen interactions at the granuloma level. Host-pathogen interactions within individual granulomas at different stages of disease have not been examined in cattle. We examined bacterial burden and cytokine expression in individual pulmonary granulomas from steers at 30, 90, 180, and 270 days after experimental aerosol infection with M. bovis. Bacterial burdens within individual granulomas examined 30 days after infection were greater and more heterogenous (variable) than those examined 90 to 270 days after infection. Bacterial burdens did not correlate with expression of IFN-γ, TNF-α, TGF-β, granuloma stage, or lung lesion score, although there was a modest positive correlation with IL-10 expression. Granuloma stage did have modest positive and negative correlations with TNF-α and IL-10, respectively. Heterogeneity and mean expression of IFN-γ, IL-10 and TNF-α did not differ significantly over time, however, expression of TGF-β at 90 days was significantly greater than that seen at 30 days after infection.

Fading elk syndrome, or chronic ill-thrift of elk, is a disease associated with abomasal parasitism with Ostertagia species, of which elk appear to be particularly susceptible. While this syndrome has been extensively reported to affect wapiti-type red deer hybrids farmed in New Zealand since the mid 1980's, there is only a single report of this disease in North America. Here, we report a case of fading elk syndrome in a herd of 34 elk (Cervus elaphus) in Ames, Iowa, at the National Animal Disease Center. Analysis of complete blood counts were unremarkable, but blood chemistry demonstrated a severe hypoalbuminemia. Fecal floatations were also unremarkable, and non-diagnostic. Histological examination of tissues collected at necropsy revealed proliferative abomasitis and nematodes consistent with Ostertagia spp. Anthelmintic treatment consisting of a combination of pour-on Cydectin® and injectable Noromectin Plus®, at double the recommended dose for cattle, showed positive results, as all remaining animals in the herd recovered. The work presented here is the first report of naturally-acquired disease in a herd of captive elk used for research and sheds light on this seldomly-reported disease in North America.

The only vaccine ever approved for human tuberculosis was developed a century ago from an isolate of Mycobacterium bovis derived from a tuberculous cow. Initial safety and efficacy studies of an attenuated version of this isolate were conducted in cattle and other animals. In 1921 the first human, an infant, was orally dosed with this attenuated strain that came to be known as M. bovis bacillus Calmette-Guérin (BCG); named for Albert Calmette and Camille Guérin, the two French scientists that developed the strain. Since 1921, billions of people have been vaccinated with BCG making it the oldest, most widely used, and safest vaccine in use today. It is also the tuberculosis vaccine most studied for use in wildlife, including deer. While BCG vaccination of deer may not reliably prevent infection, it consistently decreases lesion severity, minimizing large, necrotic lesions, which often contain large numbers of bacilli. It is believed that decreased lesion severity correlates with decreased disease transmission; however, this hypothesis remains to be proven. Safety studies in white-tailed deer show BCG may persist in lymphoid tissues for up to 12 months; a factor to be considered in deer used for food. Beyond efficacy and safety, methods of vaccine delivery to free-ranging deer are also under investigation, both in the laboratory and in the field. The ideal delivery method is effective, efficient and safe for non-target species, including livestock. Ingestion of BCG by cattle is of special concern as such cattle may present as “false positives” using currently approved diagnostic methods, thus interfering with efforts by animal health agencies to monitor cattle for tuberculosis. An effective BCG vaccine for deer would be of value in regions where free-ranging deer represent a potential source of M. bovis for livestock. Such a vaccine would also be beneficial to farmed deer where M. bovis represents a serious threat to trade and productivity.