Foal monocyte - derived dendritic cells become activated upon Rhodococcus equi infection 1

25 Susceptibility of foals to R. equi pneumonia is exclusive to the first few months of life. The 26 objective of this study was to investigate immediate immunologic response of foal and adult horse 27 antigen presenting cells (APCs) upon infection with R. equi. We measured the activation of antigen 28 presenting molecule MHC class II, co-stimulatory molecules CD40 and CD86, the cytokine IL-12 and 29 the transcriptional factor IRF-1 in monocyte-derived macrophages (mMOs) or dendritic cells (mDCs) of 30 adult horses or foals of different ages (from birth to 3 months of life) infected with virulent R. equi or its 31 avirulent plasmid-cured derivative. Infection with virulent or avirulent R. equi-induced (p ≤ 0.01) the 32 expression of IL-12p35 and IL-12p40 mRNA in foal mMOs and mDCs at different ages. This response 33 was likely mediated by the higher (p = 0.008) expression of IRF-1 in foal mDCs at birth than adult 34 horses. R. equi infection promoted comparable expression of co-stimulatory molecules CD86 and CD40 35 in foal and adult horse cells. The cytokine and co-stimulatory response by foal mDCs was not 36 accompanied by robust MHC class II molecule expression. These data suggest that foal APCs detect the 37 presence of R. equi and respond with the expression of the T H 1 inducing cytokine IL-12. Nevertheless, 38 there seems to be a limitation in the expression of MHC class II molecule, which we hypothesize may 39 compromise efficient priming of naïve effector cells in early life. 40 41 42 43 44 45 46 47