IL-6 signalling protects zebrafish larvae duringStaphylococcus epidermidisinfection in a novel bath immersion model

Abstract

The host immune responses to Staphylococcus epidermidis, a frequent cause of nosocomial infections, is 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 a marked inflammation characterised by heightened NF-B signalling and elevation of several pro-inflammatory cytokines. There is rapid upregulation of il-1b and tnf-a transcripts, while increase in il-6 levels is relatively more delayed. IL-6 signalling pathway is further amplified by elevation of IL-6 signal transducer (il-6st) levels, which is negatively-regulated by dre-miR-142-5p. Our studies describe the host immune responses to S.epidermidis infection and identifies a novel role for miR-142-5p -il-6st interaction in modulating this response.latter especially in neonates (Cheung and Otto, 2010;Nguyen et al., 2017). The high prevalence of multi-drug resistant strains, particularly in the clinical setting as well as the increasing incidence of such infections have made S.epidermidis infections a serious burden for health-care world-wide. For example, S.epidermidis alone accounts for ~22% of bloodstream infections in intensive care setting in the US, ~30% of orthopaedic-device related infections that may increase up to ~50% in developing countries, and 15-40% of prosthetic valve endocarditis (Le et al., 2018;Otto, 2009; Sabaté Brescó, Marina et al., 2017).Mechanisms of S.epidermidis biofilm formation and immune responses to the infection have been investigated in cell cultures and ex vivo models. Characterisation of host immune responses to this pathogen in vivo however has been scarce (Sabaté Brescó, Marina et al., 2017). Here we report the establishment of an in vivo zebrafish model of S.epidermidis infection. We demonstrate an early cellular response that is composed of macrophages and a subsequent immune response that activates the Tlr-2 signalling pathway. The host mounts an NF-B mediated pro-inflammatory response downstream to Tlr-2 and the microRNA miR-142-5p is involved in amplification of IL-6 signalling in this response.

Functional miR-142a-3p Induces Apoptosis and Macrophage Polarization by Targeting tnfaip2 and glut3 in Grass Carp (Ctenopharyngodon idella)

“…mir-142a-3p was one of 21 differentially expressed miRNAs between grass carp susceptible and resistant to A. hydrophila (23,51); the findings were consistent with a previous report that mir-142a-5p was involved in the regulation of the IL-6 signaling pathway, thereby modulating inflammation (52). In the present study, we focused on the function of miR-142a-3p in the inflammatory response of grass carp infected with A. hydrophila.…”

Development of zebrafish (Danio rerio) as anin vivomodel forBorrelia burgdorferiinfection

“…Survival of zebrafish through 72 hpi remained at 100% following infection in 1×10 7 spirochetes/mL B. burgdorferi suspension (Table 1), indicating no toxicity from either the immersion suspension media (BSK-H) or from B. burgdorferi . Although suspension of zebrafish in pure water or PBS would tailor to the needs of the fish [34,35,36,37], B. burgdorferi have been found to form round bodies within 10 minutes of exposure to pure distilled water [38]. By diluting BSK-H media 1:1 with zebrafish water, the spirochete morphology of B. burgdorferi was preserved throughout the 8-hour infection period (verified via darkfield microscopy of the suspensions), indicating that B. burgdorferi remained in their active, motile state.…”