Age-related changes following in vitro stimulation with Rhodococcus equi of peripheral blood leukocytes from neonatal foals.
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.
Publication Date: 2013-05-17 PubMed ID: 23690962PubMed Central: PMC3656898DOI: 10.1371/journal.pone.0062879Google Scholar: Lookup
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- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- Non-P.H.S.
Summary
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The research article discusses a study that investigated age-related changes in immune response in newborn foals when exposed to Rhodococcus equi, a bacterium causing pneumonia. The study used genomic tools to examine gene expression in the foals’ white blood cells to understand their innate susceptibility to disease.
Research Objectives and Methodology
- The primary goals of the study were to determine the differences in gene expression in stimulated and non-stimulated leukocytes in foals at specific ages and to identify how the gene expression profile changes with age when exposed to the bacterium.
- Samples of peripheral blood leukocytes were gathered from six foals at various stages: within 24 hours of birth, and at 2, 4, and 8 weeks of age.
- Each sample was divided, with half being used as a control (untreated), and the other half being exposed to the R. equi bacteria.
- RNA extraction and testing were performed to check changes in gene expression. By labelling the extracted RNA with fluorescent dyes, researchers were able to observe changes through microarray hybridisations.
Key Findings
- The study revealed age-dependent differing expression of genes related to immunity. The genes imperative for immunity against pathogens were only activated at later stages, indicating that neonatal foals might have weaker immune responses early in life.
- While foals up to the age of eight weeks showed the capacity to initiate a protective inflammatory response against the bacteria, there was lesser expression of other immune-related genes closer to birth. This suggests that their immune system might not be equipped to combat infections in early life, making them susceptible to diseases caused by the bacterium.
Implications and Conclusions
- This finding demonstrates a potential area of vulnerability in the foals’ immune defenses against R. equi infection. It also raises the prospect of new preventative or therapeutic strategies targeting these genes and pathways.
- A targeted approach can help strengthen the immune response of foals at an early age, reducing their susceptibility to diseases such as pneumonia caused by R. equi.
Cite This Article
APA
Kachroo P, Ivanov I, Seabury AG, Liu M, Chowdhary BP, Cohen ND.
(2013).
Age-related changes following in vitro stimulation with Rhodococcus equi of peripheral blood leukocytes from neonatal foals.
PLoS One, 8(5), e62879.
https://doi.org/10.1371/journal.pone.0062879 Publication
Researcher Affiliations
- Department of Veterinary Integrative Biosciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas, United States of America.
MeSH Terms
- Age Factors
- Animals
- Animals, Newborn / immunology
- Animals, Newborn / microbiology
- Gene Expression Profiling / veterinary
- Gene Expression Regulation / physiology
- Horse Diseases / immunology
- Horse Diseases / microbiology
- Horses
- Leukocytes / microbiology
- Pneumonia, Bacterial / immunology
- Pneumonia, Bacterial / veterinary
- Protein Array Analysis / veterinary
- Real-Time Polymerase Chain Reaction
- Rhodococcus equi
Conflict of Interest Statement
The authors have declared that no competing interests exist.
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Citations
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