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

The 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. Macrophages play a primary role in the host immune response and are involved in clearance of infection in the larvae. S.epidermidis infection activates Tlr−2 signalling pathway by upregulation of tlr−2. There is marked inflammation characterised by heightened NF−κB signalling and elevation of several pro−inflammatory cytokines. Infected larvae show rapid upregulation of il−1b and tnf−a transcripts, while increase in il−6 levels is relatively more delayed. 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. Heightened IL−6 signalling is physiologically relevant 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 novel role for miR−142−5p − il−6st interaction in modulating this response and establishes the importance of IL−6 signalling in this infection model.