Age-related changes following in vitro stimulation with Rhodococcus equi of peripheral blood leukocytes from neonatal foals.
Authors: Kachroo Priyanka, Ivanov Ivan, Seabury Ashley G, Liu Mei, Chowdhary Bhanu P, Cohen Noah D
Journal: PloS one
Summary
Rhodococcus equi causes a devastating pyogranulomatous pneumonia in young foals, yet the molecular basis for age-dependent susceptibility to infection remains poorly understood. Using gene expression microarrays on peripheral blood leukocytes from six foals sampled at day 1, 2 weeks, 4 weeks, and 8 weeks of age—with samples either stimulated with virulent R. equi or left unstimulated as controls—researchers characterised how the immune response matures across these critical early weeks. Key findings revealed significant age-related differential expression of immunologically important genes, notably delayed upregulation of MHC class II molecules until later time-points rather than at birth, alongside relatively diminished expression of various other immune-related genes in neonatal samples despite foals being capable of mounting some protective inflammatory response by 8 weeks. These results suggest that the heightened disease susceptibility observed in very young foals stems from genuinely incomplete immune maturation rather than complete immunological failure, identifying potential therapeutic targets—such as early MHC class II induction—that could be manipulated to improve neonatal defence against R. equi infection. For practitioners managing foals in the critical first weeks of life, this work provides molecular grounding for understanding why early-life R. equi infection remains such a clinical challenge and hints at which immunological pathways might warrant manipulation through vaccination, immunomodulation, or colostral optimisation strategies.
Read the full abstract on PubMed
Practical Takeaways
- •Newborn foals have inherently reduced immune gene expression that may explain their higher susceptibility to R. equi; protective immune responses develop progressively over the first 8 weeks of life
- •Early-life infection risk appears highest in the first 1-2 weeks when MHC class II and other immune genes are not yet upregulated — timing aligns with clinical observations of neonatal R. equi disease
- •These molecular pathways could be targets for future preventative strategies (vaccines, immune-boosting therapies) in high-risk foals, though clinical translation remains to be developed
Key Findings
- •MHC class II genes showed induction only at later timepoints (2-8 weeks), not at birth, suggesting delayed adaptive immune response development
- •Foals up to 8 weeks of age can initiate protective inflammatory response against R. equi despite age-related gene expression differences
- •Gene expression profiles show age-related differential expression in immune response pathways, with relatively decreased expression of immune-related genes closer to birth
- •Identified molecular mechanisms underlying inherent susceptibility of neonates to R. equi infection through microarray analysis of stimulated blood leukocytes