IL-6 signalling protects zebrafish larvae during Staphylococcus epidermidis infection in a novel bath immersion model

Abstract

Host immune responses to Staphylococcus epidermidis, a frequent cause of nosocomial infections, are not well understood. We have established a novel bath immersion model of this infection in zebrafish larvae. S.epidermidis infection activates Tlr-2 signalling pathway by upregulation of tlr-2. Macrophages play a primary role in the host immune response and are involved in clearance of infection in the larvae. There is marked inflammation characterised by heightened NF-{kappa}B signalling and elevation of several pro-inflammatory cytokines. Infected larvae show rapid upregulation of il-1b and tnf-a transcripts and relatively slower elevation of il-6 transcription. The IL-6 signalling pathway is additionally subject to amplification by elevation of IL-6 signal transducer (il-6st) levels, which negatively correlates with miRNA dre-miR-142-5p expression. Enhanced IL-6 signalling is protective to the host in this model as inhibition of the signalling pathway resulted in increased mortality upon S.epidermidis infection. Our study describes the host immune responses to S.epidermidis infection, identifies a likely role for miR-142-5p - il-6st interaction in modulating this response and establishes the importance of IL-6 signalling in this infection model.