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The Effect of Age on Equine Dendritic Cell Interactions With Rhodococcus equi
Department of Veterinary Sciences
Rhodococcus equi is considered the most common cause of severe pneumonia in young foals and remains one of the most important challenges to the equine industry. Current control methods for R. equi are expensive, inconvenient, and not always effective.
There is no effective vaccine against R. equi pneumonia of foals. The relative immaturity of the foal's immune system and the fact that initial exposure to the bacterium likely occurs in the first weeks of life diminish the prospects for developing an effective vaccine. Alternative strategies, including non-specifically enhancing the resistance of foals to this infection, are needed.
We have determined that part of the susceptibility of foals to this infection likely involves their inability to produce interferon-gamma, a key cytokine needed for resistance to this infection. Here we propose to identify the underlying mechanism responsible for this defect. Our approach is to examine the functionality of those cells which play a key role in regulating interfeorn-gamma production in the lung. Once the source of the defect in their ability to induce interferon-gamma is identified, a therapeutic approach to overcome this deficiency and increase interferon-gamma expression in foals might be found.
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-g 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. Therefore, we compared IFN-g expression by both peripheral blood mononuclear cells (PBMC) and bronchoalveolar lavage (BAL) cells from foals kept in the two different environments.
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.
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. Stimulation of the PBMC to cause their proliferation likewise enhances IFN-g production, which is consistent with the notion that an epigenetic mechanism is involved. Future studies will focus on this possible mechanism.
Sun L, Adams AA, Betancourt A, Stewart JC, Liu C, Horohov DW. 2012. The role of proliferation in the regulation of interferon gamma (IFNγ) expression in foals. Dev Comp Immunol 36, 534-539
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