Environmental Cues Modulate Microglial Cell Behaviour upon Shiga Toxin 2 from Enterohemorrhagic Escherichia Coli Exposure

DUHALDE VEGA M,; BERDASCO, CLARA; GOLSTEIN, JORGE; ROSATO-SIRI, MARIA VICTORIA

Frontiers in Cellular and Infection Microbiology

Frontiers Media

Año: 2020 vol. 9 p. 442 - 458

2235-2988

Shiga toxin (Stx) produced by enterohemorrhagic E. coli produces hemolytic uremicsyndrome and encephalopathies in patients, which can lead to either reversibleor permanent neurological abnormalities, or even fatal cases depending on thedegree of intoxication. It has been observed that the inflammatory componentplays a decisive role in the severity of the disease. Therefore, the objective of thiswork was to evaluate the behavior of microglial cell primary cultures upon Stx2exposure and heat shock or lipopolysaccharide challenges, as cues which modulatecellular environments, mimicking fever and inflammation states, respectively. In thesecontexts, activated microglial cells incorporated Stx2, increased their metabolism,phagocytic capacity, and pro-inflammatory profile. Stx2uptake was associated toreceptor globotriaosylceramide (Gb3)-pathway. Gb3 had three clearly distinguishabledistribution patterns which varied according to different contexts. In addition, toxin uptakeexhibited both a Gb3-dependent and a Gb3-independent binding depending on thosecontexts. Altogether, these results suggest a fundamental role for microglial cells inpro-inflammatory processes in encephalopathies due to Stx2 intoxication and highlightthe impact of environmental cues.