Project Number:
Researchers: Gasbarre, L. C.; Fleming, M. W.; Zarlenga, D. S.
Start Date: 07-Dec-93
End Date: 06-Dec-98
Performing Institution: BELTSVILLE AGR RES CENTER

Research Objectives: 1) Characterize cellular immune responses in resistant and non-resistant cattle; (2) identify helminth parasite antigens and parasitic stages that control protective immunity in cattle; (3) identify genes and gene markers that correlate with immunological resistance; (4) define immuno-regulatory factors associated with O. ostertagi.

Approach: T lymphocyte responses and cytokine induction will be defined in resistant and susceptible cattle identical at their BoLA class I and class II alleles. Cattle showing genetically controlled resistance will be used to elucidate the mechanisms of protective immunity to O. ostertagi (OST) and to identify genes controlling resistance. The role of different life cycle stages of O. ostertagi, especially hypobiotic third-stage larvae, in the generation of protective immunity will be determined. Antigens derived from or secreted by OST will be assessed for their ability to induce protective and fecundity-reducing immunity. The effect of stress on immunity to OST and the stressor effect of OST on host immune responses to vaccination or resistance to infection will be evaluated. Management procedures will be assessed for the induction of immune responses that reduce disease transmission and lessen dependence on anthelmintics. Beltsville, MD, B-1002, BL-1/BL-2, Appr.

Progress: Gastrointestinal nematodes of cattle cost beef and dairy producers in excess of \$2 billion per year as a result of decreased productivity and costs associated with treatment and altered management practices. Current control practices require the continual use of anthelmintics. Because of the appearance of drug-resistant parasite strains in other parts of the world, and the increasing concern of consumers in the US for the presence of drug residues in their food and the environment, new plans must be predicated on integrated control practices. A major component will be the use of the host immune system to better control infection, and enhance the overall well-being of the animal.

In the past year, we cloned and characterized transcription of transforming growth factor (TGF), interleukin 13 (IL13), IL5, and tumor necrosis (TNF) to add to the extensive panel of important bovine cytokines previously described. Used RT-PCR to characterize local immune responses to Ostertagia ostertagi and Haemonchus placei in naive and immune cattle, and to Cryptosporidium parvum in neonatal calves. Showed that Ostertagia induces stereotypic anti-nematode responses, but these responses do not protect cattle from a challenge infection. Conversely, Haemonchus induces much less apparent responses, but the responses do protect from reinfection. Demonstrated that in part this may be due to an inactivation of immune effector cells in the mucosal tissues.

These results indicate that the proper means of protecting cattle from Ostertagia reinfection would be to down-regulate the parasite’s ability to produce the immunosuppressive materials. Showed that Cryptosporidia infections of neonatal calves result in a rapid and marked increase in the induction of Interferon-gamma (IFNg), indicating that protection of the neonate may require an early induction of IFNg by non-specific immunomodulators. Trickle inoculations of Ostertagia ostertagi in dairy calves resulted in higher peripheral concentrations of cortisol and reduced adrenal responsiveness to ACTH.

Furthermore, the combined effects of chronic parasite-induced stress with acute transportation-induced stress resulted in elevated cortisol levels, behavioral modifications, and elevated concentrations of Pasteurella bacteria in the lungs, the primary agent of shipping fever. Such synergistic stressors appear to negatively impact animal well-being. Identified a method based on differential enzymatic amplification of parasite genomic DNA to diagnose and quantitate Ostertagi eggs in feces of infected animals. Because this parasite is the dominant pathogen in the US, with no present accurate means to quantify infection levels, this method may be important for the development of effective integrated control programs. Overall, these studies will enable scientists to develop novel biological control methods for cattle parasitic infections.


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