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Interferon Gamma Regulation in the Foal
Department of Veterinary Sciences
Respiratory diseases remain one of the major impediments to the equine industry. Young foals, in particular, suffer frequently and severely from viral and bacterial infections of the respiratory tract. Rhodococcus equi, in particular, remains the most common cause of subacute or chronic abscessating bronchopneumonia in young foals. Epidemiological and experimental data indicate foals less than 1 month of age are at greatest risk for infection.
The underlying hypothesis of this research project is that the decreased production of interferon-gamma by young foals contributes to their susceptibility to infection with Rhodococcus equi and other intracellular pathogens. We have already demonstrated that young foals are most deficient at interferon-gamma production at the time when R. equi exposure likely occurs. Here we propose to analyze cytokine mRNA expression in a large population of foals from multiple farms that have a high incidence of R. equi infections. We also will investigate possible approaches to enhance interferon-gamma production in the foal and thereby increase resistance to infection.
2011 Project Description
Interferon-gamma (IFN-g plays an important role in innate and adaptive immune responses by activating macrophages and NK cells. It is also critical for the induction of adaptive immunity by promoting T cells differentiation and B cells activation. Decreased IFN production is associated with susceptibility to infectious disease.
In very young foals, IFN-g expression is deficient when compared to older foals and adults. This diminished production of IFN-g coincides with the peak susceptibility of foals to infection with Rhodococcus equi. While the underlying mechanism responsible for this deficiency in IFN-g production remains unknown, the immunological naivety of neonates likely plays a role. Exposure to environmental microbial antigens has been shown to promote IFN-g production in neonatal mice and humans. Whether environmental exposure to microbial antigens has a similar effect on IFN-g production in neonatal foals was unknown.
A total of 32 healthy pony foals born over a two year period were used for this study. Sixteen of the foals were chosen randomly at birth to spend 4 hours a day for 3 days (MWF) of each week in individual stalls with their mares. The stalls were not cleaned during the study period. This barn exposure started when the foals were less than 1 week old and stopped after they reached 2 months of age. When not in the barn, the foals were kept on pasture with 16 other foals and their mares that remained on pasture throughout the study. Air samples were collected from both the barn and the pasture at the beginning and end of the study period. We then compared IFN-g expression by both peripheral blood mononuclear cells (PBMC) and bronchoalveolar lavage (BAL) cells from pony foals kept in the two different environments. As expected, there were significantly more culturable bacterial colonies, both gram+ and gram-, as well as fungi collected in the air samples from the barn compared to the pasture.
While exposure to microorganisms in the air of the barn did not induce recruitment of more lymphocytes into the lung of the foals, exposure did increase the frequency of IFN-g + lymphocytes amongst BAL cells. There was also an increased percentage of IFN-g+ lymphocytes in the peripheral blood in those foals exposed to barn air. The effect of barn air on IFN-g production likely reflects the multiple and various microbial components it contains. The mechanism whereby exposure to barn air promotes the increase in IFN-g expression is unknown. One possibility is that environmental effects on gene expression occur via epigenetic regulation. Future studies will need to focus on these possible mechanisms.
The underlying theory that environmental exposures to microbial antigens affects the development of the immune system, referred to as the hygiene hypothesis, was first introduced two decades ago. This hypothesis postulated that exposure to environmental microbial components reduced the risk of allergic disease in humans. This theory has been widely supported by epidemiological studies and laboratory research. However, little is known about the underlying mechanism involved in this process. Even less is known about the effect of environmental microbial exposure on immune development in non-human species.
Here, we have shown that exposure to environment microbial components can affect the expression of interferon-gamma and could alter the susceptibility of foals to infectious diseases. Thus, we have extended the hygiene hypothesis to include not only reduced susceptibility to allergic disease but increased resistance to infectious diseases, such as Rhodococcus equi-caused pneumonia in foals.
Sun L, Adams AA, Page AE, Betancourt A, Horohov DW. 2011. The effect of environment on interferon-gamma production in neonatal foals. Vet Immunol Immunopathol 143: 170-5