earticle

영어

Shigellosis caused by Shiga toxin (Stx)-producing Shigella dysenteriae serotype 1 or Stx-producing Escherichia coli (STEC) continues to be a major public health threat and is a particular concern because of the potential to develop life-threatening extra-intestinal complications such as acute renal failure (hemolytic uremic syndrome; HUS) and CNS complications such as seizures, paralysis, and death. Once Shiga toxins (Stxs) are internalized following the toxin-specific receptor (globotriaosylceramide, Gb3) binding on host cellular surface, they are trafficked into the Golgi apparatus and to the ER in retrograde manner to enter the host cell cytosol, leading to various host cellular responses including protein synthesis inhibition, apoptosis through ER stress, autophagy and inflammation associated with the toxin-containing exosome secretion. The distinct investigations on host cell signaling responses activated by Stxs as multi-functional proteins were performed to identify novel targets for intervention in pathogenesis by employing various in-vitro/in vivo models including human renal three dimensional spheroid or organoid. Different forms of circulating Stx2a have been described: either alone as Stx2a in microvesicles shedding from blood cells, or as Stx2a associated with human neutrophil. In addition to this, alternative non canonical receptors to Stx have been proposed whereby the toxin can bind to a host cell. Moreover, many studies present compelling and strong evidences about therapeutic applications to target particular diseases such as tumors by engineering the toxins. In this meeting, we will cover diverse aspects of interactions between host cells mainly focusing on renal tissue, Shiga toxins, and the bacteria that produce the toxins.