Grants and Contracts Details
Description
The vulnerability of foals to specific pathogens such as Rhodococcus equi is believed to reflect an innate
immunodeficiency, the nature of which remains poorly understood. We have shown that very young foals
exhibit a deficit in their ability to produce interferon-gamma (IFN-y), a key cytokine required for resistance to
R. equi. Given the central role dendritic cells (DC) play in regulating IFN-y responses, we propose that DC
,obtained from foals will have phenotypic and functional differences from those derived from adult horses. We
have recently reported that monocyte-derived DC (MoD C) from foals differ from MoDC from adults. This
functional immaturity of foal MoDC was evidenced by altered surface marker expression and decreased
cytokine gene transcription. Since inhalation likely represents the primary means of exposure to R. equi, it is
important to assess the functional status of pulmonary DC. Our central hypothesis is that immaturity of foal DC
contributes to their inability to produce IFN-y and their increased susceptibility to infection with R. equi. Here
we propose to further characterize the pulmonary DC of foals and adult horses and compare them to MoDC in
terms of their responses to lipopolysaccharide (LPS, endotoxin) and R. equi (Specific Aim 1). Our expectation
is that foal pulmonary DC will exhibit altered patterns of both cell surface antigen expression and cytokine
production. We will also assess the effect of in vivo exposure to LPS on DC maturation and function (Specific
Aim 2) as this may represent a contributing factor to the foal's susceptibility to R. equi infection. Our
expectation is that there will be significant differences between foal and adult pulmonary DC responses to this
exposure. While initial interaction between R. equi and the innate immune system are viewed as critical
determinants in determining the ultimate consequence ofthe infection, no information is available regarding the
interaction between this microbe and equine pulmonary DC. This study will address an early event in the
interaction between bacterium and host that could play a central role in susceptibility to infection.
Status | Finished |
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Effective start/end date | 2/15/10 → 2/14/13 |
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