Human neutrophils secrete IL-1beta upon infection with Shiga toxin-producing Escherichia coli

SHIROMIZU, CAROLINA MAIUMI; SABBIONE F; KEITELMAN I; RAMOS MV; MIGLIO RODRIGUEZ M; GUZMAN M; GALLETTI J; JANCIC C; PALERMO M; TREVANI AS

Congreso; LXVI Reunión Anual de la Sociedad Argentina de Inmunología. Mar del Plata 14-17 de noviembre, 2018, Argentina.; 2018

Sociedad Argentina de Inmunología

Shiga toxin-producing E coli (STEC) infections can cause diseasewith diverse severity, from bloody diarrhea (hemorrhagic colitis) tohemolytic uremic syndrome (HUS), a life-threatening condition. HUSis characterized by hemolytic anemia, thrombocytopenia and renalfailure, triggered by Shiga toxin (Stx). STEC are non-invasive bacteria that colonize the intestine where they release Stx that then reaches the bloodstream; an event that might be facilitated by damagesin the intestinal mucosa and promoted by inflammation. Given thatneutrophils (PMN) are recruited to the intestine after the infection,our aim was to determine if these cells can contribute to the localinflammation by secreting IL-1β. We employed PMN isolated fromperipheral blood of healthy donors. These cells were incubated withStx-producer E coli O157:H7 (E coli Stx+) or with the Stx-non-producer bacteria (E coli Stx-) and 4hs later we determined IL-1β levelsin the supernatants by ELISA. PMNs secreted IL-1β in similar levelsin response to both strains when incubated at MOI of 0.05 (1232±51pg/ml vs 1293±32 pg/ml; PMN+E coli Stx+ vs PMN+E coli Stx- respectively, n=4) and at MOI of 1 (n=3). IL-1β secretion by PMN incubated with E coli Stx- was not modulated by addition of Stx type2 (Stx2; 0.1 μg/ml). In addition, there were no differences betweenthe levels of IL-1β secreted in response to the culture supernatantsof both strains (n=2). In accordance to these observations, Stx2 wasunable per se of inducing IL-1β secretion or of modulating the secretion induced by PAM3CSK4 (a TLR2/1 agonist)+ATP. In conclusion,PMN secrete IL-1β in response to E coli O157:H7, but this propertyis neither dependent nor is modulated by Stx. These findings suggest that PMN might contribute to the pathology by increasing thelocal inflammation through the secretion of IL-1β.