Human neutrophils release IL-1 beta in response to Enterohaemorrhagic E. coli.

SHIROMIZU, CAROLINA MAIUMI; SABBIONE FLORENCIA; KEITELMAN, IRENE; ROSATO MICAELA; RAMOS MV; JANCIC, CAROLINA C.; GALLETTI, JEREMÍAS; PALERMO M; TREVANI, ANALÍA SILVINA

Simposio; Virtual International Symposium Neutrophil 2021; 2021

The enteric pathogen Shiga toxin (Stx)-producing Escherichia coli (STEC) remains a major public health concern because it can cause from bloody diarrhea (hemorrhagic colitis) to hemolytic uremic syndrome (HUS), a disease that in Argentina is the most common cause of acute renal failure in early childhood. HUS is characterized by hemolytic anemia, thrombocytopenia, and renal failure, that are triggered by the Shiga toxin (Stx). There are no vaccines or therapies to prevent or treat STEC-caused diseases. We aim to understand the role of neutrophils (PMN) in the inflammatory response induced by both the bacteria and Stx, that contribute to the tissue damage that leads to HUS development.STEC are non-invasive bacteria that colonize the intestine where they release Stx that then reaches the blood stream; an event that appears to be facilitated by damages in the intestinal mucosa and promoted by inflammation. Given that PMNs are recruited to the intestine in response to STEC infections, our aim was to evaluate the ability of E. coli to stimulate neutrophils to produce IL-beta. By employing highly purified PMNs isolated from peripheral blood of healthy donors and the Stx-producer E coli O157:H7 (E coli Stx+), the isogenic Stx-non-producer bacteria (E coli Stx-) or a non-pathogenic E. coli strain (C600), we found that all the bacteria stimulated PMNs to secrete IL-1beta. However, both E coli O157:H7 strains triggered the release of similar levels of IL-1beta levels and higher than the non-pathogenic bacteria. IL-1beta secretion was not associated to lytic PMN death and was only observed in significant levels with live- but not heat-killed bacteria.Our findings suggest that neutrophils might also contribute to the intestinal inflammatory response triggered by STEC infections by releasing IL-1beta. Further studies are ongoing in our laboratory to determine the mechanisms involved in this secretion.