The Effect of Age on Equine Dendritic Cell Interactions with Rhodococcus Equi

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.