Immune Response of Young Foals Exposed to Rhodococcus

  • Horohov, David (PI)

Grants and Contracts Details


Abstract of Research Plan In Scientific Terms: Scientific Importance: State the hypothesis of the project clearly with specific aims itemized and chronology projected. Briefly summarize past progress, and state the long-term goals of the project, and describe concisely the methodology for achieving these goals. The abstract should be a succinct, accurate and self-explanatory description of the proposed work. The development of immunological responses in newborn animals of all species, including the horse, is poorly understood. Clinical evidence suggests that very young foals are permissive to a number of bacterial and viral infections despite the presence of maternal immunoglobulins. The unique susceptibility of young foals to infection with Rhodococcus equi is a well-recognized example of this age-dependent phenomenon. Yet even on endemic farms, some foals develop R. equi pneumonia and others do not though presumably all foals are exposed to the organism. While it remains unknown as to what host factors determine the outcome of exposure, it is clear that cell-mediated immunity plays a critical role in resistance to R. equi. Thus protection against R. equi is known to be Thl-mediated. We have already shown that young foals exhibit a bias towards Th2 immune response. The factors regulating this bias are unknown. We hypothesize that young foals who develop Rhodococcal pneumonia will have a pattern of cytokine gene expression indicative of a Th2-bias whereas other foals also exposed but who do not develop the disease will exhibit signs of a Thl-response. Further we propose that exposure to R. equi may in itself promote the development ofThl immune responses. To test this hypothesis, we will monitor the cytokine profile of a group of at-risk foals on a commercial breeding farm that has a recent history of high-incidence Rhodococcus infections and compare the profile of infected foals with those that are exposed but not infected. We will continue to monitor these same foals following their exposure to R. equi in order to determine its effect on the cytokine profile in the exposed foal. Importance to the Equine Industry: State the significance of the problem being investigated to the industry, the relevance of this project to that problem and the realistic expectations of what effect this project will accomplish, in relevance to the problem. Respiratory diseases remain a persistent management problem for the equine industry, particularly among young animals. Rhodococcus equi is considered the most common cause of subacute or chronic abscessating bronchopneumonia in foals less than 5 months of age. Foals exhibit a unique age-dependent susceptibility to this infection. While this is thought to be the result of a failure of the foal's immune response to clear this agent, the precise mechanism for this defect is unknown. We have previously characterized the cell mediated immune responses of foals by measuring the production ofT cell cytokines. Our results showed that young foals exhibit a deficit in their ability to produce those cytokines that are required for resistance to R. equi. Here we propose to assess the effect of this bias on the susceptibility of foals for developing rhodococcal pneumonia. We will monitor a population of foals in a production setting that has had a significant problem with rhodococcal pneumonia. Our prediction is that those foals with the so-called Th2 cytokine bias will be most at risk for developing rhodococcal pneumonia whereas those with a Thl-bias will be resistant to disease. If we are able to demonstrate an association between the cytokine bias of the foal with disease susceptibility it may then be possible to propose immunomodulatory approaches that may alter this response and increase the resistance of the foals. ABSTRACT OF RESEARCH PLAN IN LAY LANGUAGE: Describe the research plan in lay terms. This page should be shorter and less detailed than the previous page. This abstract will be used to explain your research to the directors of the foundation, the press, the general public, and potential donors. Newborn foals are faced with a number of challenges after birth including exposure to infectious and opportunistic pathogens. While maternal antibodies provide some protection until the foal's oWn immune system is able to deal with these challenges, young foals exhibit unique susceptibilties to respiratory infections particularly those caused by the bacterium Rhodococcus equi. This bacterium causes a severe pneumonia in young foals. As the foals age they become resistant to this disease, though the reason for this age-dependent susceptibility reamins unclear. The goal of this project is to characterize the immune response of foals that are expsoed to Rhodococcus equi in their environment in order to identify those components that may be imortant in determining susceptibility or resistance to this agent. INDUSTRY IMPORTANCE: Describe the importanc~ of the proposed project to the equine industry in lay terms. Rhodococcus equi is considered the most common cause of severe pneumonia in young foals and remain one of the most important challenges to the equine industry. While significant efforts have focused on the pathogenic characteristics of this bacterium, little is known regarding the reason for the particular susceptibility of young foals to this disease. The goal of this research is to better characterize the immunological status of the young foals that are exposed to this bacterium in order to identify which immunological responses may be important in conferring susceptibility or resistance to this disease.
Effective start/end date4/1/053/31/07


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