Proinflammatory cytokine responses of cultured equine keratinocytes to bacterial pathogen-associated molecular pattern motifs.
Authors: Leise B S, Yin C, Pettigrew A, Belknap J K
Journal: Equine veterinary journal
Summary
# Editorial Summary Keratinocytes form the horse's first line of defence against bacterial infection, yet their capacity to recognise different bacterial pathogens remains poorly characterised. Leise and colleagues cultured primary equine keratinocytes and exposed them to five pathogen-associated molecular patterns (PAMPs) representing both Gram-negative and Gram-positive bacteria, measuring inflammatory cytokine production (IL-1β, IL-6, CXCL8 mRNA) at 4 and 24 hours via quantitative PCR. Only lipopolysaccharide (LPS, a Gram-negative marker) and flagellin triggered significant cytokine upregulation, whilst peptidoglycan, lipoteichoic acid and bacterial DNA produced no response—indicating equine keratinocytes possess functional TLR4 and TLR5 signalling but lack functional TLR2, TLR9 and NOD1/2 pathways. This molecular asymmetry may explain the clinically observed pattern of greater epidermal damage in Gram-negative sepsis cases, where keratinocytes can mount a robust pro-inflammatory response, compared to Gram-positive infections where the epithelial barrier remains immunologically "silent" and potentially compromised. For practitioners managing septic conditions, these findings suggest that epidermal involvement may correlate with pathogen type, though further research on in vivo keratinocyte responses and the role of other cell types in the dermal–epidermal interface is warranted.
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Practical Takeaways
- •Equine skin appears more susceptible to inflammatory damage during Gram-negative bacterial sepsis due to robust keratinocyte TLR4/TLR5 activation, which may inform monitoring and treatment priorities in septic cases
- •The differential immune response of equine keratinocytes to bacterial types suggests that sepsis management strategies may need pathogen-specific approaches to minimize epidermal complications
- •Clinical observations of worse epidermal complications in Gram-negative sepsis now have a mechanistic explanation at the cellular level, supporting targeted anti-inflammatory interventions in these cases
Key Findings
- •Equine keratinocytes showed significant increases in IL-1β, IL-6, and CXCL8 mRNA in response to LPS (Gram-negative PAMP) at 4 hours compared to controls (P<0.05)
- •Flagellin exposure induced significant IL-6 and CXCL8 mRNA increases, indicating functional TLR5 signalling in equine keratinocytes
- •No significant cytokine expression occurred following LTA, peptidoglycan, or CpG exposure, indicating lack of functional TLR2, TLR9, and NOD signalling
- •Equine keratinocytes demonstrate selective responsiveness to Gram-negative bacterial PAMPs over Gram-positive PAMPs, potentially explaining increased epidermal injury in Gram-negative sepsis