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

KEITELMAN, IRENE A; GUZMÁN, MAURICIO; PALERMO, MARINA; SABBIONE, FLORENCIA; MIGLIO RODRIGUEZ, MAXIMILIANO; JANCIC, CAROLINA C.; SHIROMIZU, CAROLINA MAIUMI; RAMOS, MARÍA VICTORIA; GALLETTI, JEREMÍAS; ANALÍA, TREVANI S.

Mar del Plata

Congreso; 66 Reunión Anual de la Sociedad Argentina de Inmunología; 2018

SAI - SAIC

Shiga toxin-producing E coli (STEC) infections can cause disease with diverse severity, from bloody diarrhea (hemorrhagic colitis) to hemolytic uremic syndrome (HUS), a life-threatening condition. HUS is characterized by hemolytic anemia, thrombocytopenia, and renal failure, 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 damages in the intestinal mucosa and promoted by inflammation. Given that neutrophils (PMN) are recruited to the intestine after the infection, our aim was to determine if these cells can contribute to the local inflammation by secreting IL-1β. We employed PMN isolated from peripheral blood of healthy donors. These cells were incubated with Stx-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 levels in the supernatants by ELISA. PMNs secreted IL-1β in similar levels in response to both strains when incubated at MOI of 0.05 (1232±51 pg/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 the addition of Stx type 2 (Stx2; 0.1 μg/ml). In addition, there were no differences between the levels of IL-1β secreted in response to the culture supernatants of both strains (n=2). In accordance to these observations, Stx2 was unable per se of inducing IL-1β secretion or of modulating the secretion induced by PAM3CSK4 (a TLR2/1 agonist)+ATP. In conclusion, PMN secretes IL-1β in response to E coli O157:H7, but this property is neither dependent nor is modulated by Stx. These findings suggest that PMN might contribute to the pathology by increasing the local inflammation through the secretion of IL-1β.