Effects of Separate and Concomitant TLR-2 and TLR-4 Activation in Peripheral Blood Mononuclear Cells of Newborn and Adult Horses.
Authors: Vendrig Johannes Cornelis, Coffeng Luc Edgar, Fink-Gremmels Johanna
Journal: PloS one
Summary
Neonatal foals are significantly more vulnerable to bacterial infection than adult horses due to an immature innate immune response, with toll-like receptors (TLRs) playing a central role in bacterial recognition and triggering appropriate immune defences. Researchers isolated peripheral blood mononuclear cells from both adult horses and foals, then stimulated them separately and in combination with TLR-2 and TLR-4 ligands to assess whether activating TLR-2 could modulate the inflammatory cascade triggered by TLR-4, using Bayesian hierarchical modelling to account for inter-individual variation. Foal immune cells demonstrated markedly suppressed cytokine responses overall compared with adults; critically, whilst TLR-2 activation significantly enhanced interleukin-10 production in adult horse cells when combined with TLR-4 stimulation (suggesting a potential immune-dampening mechanism), this anti-inflammatory effect was absent in foal cells, and TLR-2 activation did not reduce the pro-inflammatory lipopolysaccharide response in either age group. These findings indicate that immunological mechanisms documented in other species cannot be assumed to translate to equines, emphasising the fundamental biological differences in foal immune maturation and highlighting a significant gap: current TLR-2 activation strategies do not enhance bacterial defence in young horses. The work underscores an urgent need to identify alternative approaches—whether pharmacological, nutritional, or immunological—to boost foal immune competence during the critical early-life period when susceptibility to sepsis remains dangerously high.
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Practical Takeaways
- •Foals have fundamentally different immune responses to bacterial challenges than adults; therapeutic strategies proven effective in other species may not work in horses and require species-specific validation
- •Current TLR-based immunomodulation approaches (e.g., TLR-2 agonists) are unlikely to enhance foal resistance to infection without additional research into equine-specific immune mechanisms
- •Enhanced biosecurity and passive immunity strategies remain critical in neonatal foal management, as immunological interventions targeting TLRs may not improve bacterial defense as expected
Key Findings
- •Foal PBMCs showed lower overall cytokine responses compared to adult horse PBMCs
- •TLR-2 activation did not suppress TLR-4-mediated inflammatory responses in foal PBMCs, unlike in other species
- •Adult horse PBMCs upregulated TLR-2 and downregulated TLR-9 following TLR ligand activation, but foal PBMCs did not
- •Concomitant TLR-2 and TLR-4 activation increased interleukin-10 production in adult horses but not foals