Enhanced activation of Gb3-bound Shiga toxin by leptin induced after infection with STEC O157

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Oral infection with Shiga toxin (Stx) -producing E. coil resulted in acute encephalopathy in protein malnutrition mice. The infection induced TNF-α and leptin in the blood of infected mice within 18 h of infection. After the elevation of these two soluble factors in the blood, the number of apoptotic cells in the brain increased. In contrast, infection with Stx-nonproducing E. coli did not induce such changes. Treatment with leptin induced high levels of TNF-α and NO production from cultured neuronal cells after incubation with Stx. Treatment with leptin caused the increase in ABCA1 in non-rafts of TNF-α-stimulated neuronal cells, which was associated with the increase in Gb3 molecules in lipid rafts as well as endocytosis of Gb3-bound Stx by the cells. These changes seemed to be related to the enhancement of Stx-induced apoptosis of neuronal cells. However, such enhancement was not observed for endovascular cells. The present findings may account for the different sensitivity to STEC infection among individuals, though the precise mechanism of how leptin increases Stx sensitivity of neuronal cells.