Abstract
Rhodococcus equi is an intracellular bacterium primarily known as an equine pathogen that infects young foals causing a pyogranulomatuous pneumonia. The molecular mechanisms mediating the immune response of foals to R. equi are not fully elucidated. Hence, global genomic high-throughput tools like gene expression microarrays might identify age-related gene expression signatures and molecular pathways that contribute to the immune mechanisms underlying the inherent susceptibility of foals to disease caused by R. equi. The objectives of this study were 2-fold: 1) to compare the expression profiles at specific ages of blood leukocytes from foals stimulated with virulent R. equi with those of unstimulated leukocytes; and, 2) to characterize the age-related changes in the gene expression profile associated with blood leukocytes in response to stimulation with virulent R. equi. Peripheral blood leukocytes were obtained from 6 foals within 24 hours (h) of birth (day 1) and 2, 4, and 8 weeks after birth. The samples were split, such that half were stimulated with live virulent R. equi, and the other half served as unstimulated control. RNA was extracted and the generated cDNA was labeled with fluorescent dyes for microarray hybridizations using an equine microarray. Our findings suggest that there is age-related differential expression of genes involved in host immune response and immunity. We found induction of genes critical for host immunity against pathogens (MHC class II) only at the later time-points (compared to birth). While it appears that foals up to 8-weeks of age are able to initiate a protective inflammatory response against the bacteria, relatively decreased expression of various other immune-related genes points toward inherent diminished immune responses closer to birth. These genes and pathways may contribute to disease susceptibility in foals if infected early in life, and might thus be targeted for developing preventative or therapeutic strategies.
Highlights
Rhodococcus equi is a gram-positive, facultative, intracellular pathogen that primarily infects macrophages [1]
Number of Differentially Expressed Genes Comparison of the stimulated versus unstimulated peripheral blood leukocytes at day 1 (D-1) showed that 125 genes were differentially expressed, of which 89 were up-regulated and 36 down-regulated (Table 1, D-1)
We characterized the age-related gene expression profile of neonatal foals during the first 8 weeks of life associated with stimulation of peripheral blood leukocytes by R. equi
Summary
Rhodococcus equi is a gram-positive, facultative, intracellular pathogen that primarily infects macrophages [1]. The age at which foals develop R. equi pneumonia remains unknown, epidemiological and clinical evidence indicate that foals are likely infected very early in life [7,8]. This evidence is consistent with the insidious development of clinical signs in most affected foals [5], and the time required for development of large, pyogranulomatous lesions caused by R. equi. Evidence exists that the systemic immune system of newborn foals is diminished relative to more mature foals and horses, including both innate and adaptive responses to R. equi [9,10,11]. The relatively diminished immune responses of newborn foals may predispose them to infection with R. equi during early life
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