Human Neutrophils secrete IL-1b upon infection with Shiga-toxin-producing Escherichia coli

F SABIONE; M MIGLIO RODRIGUEZ; C JANCIC,; SHIROMIZU; MV RAMOS; JG GALETTI; IA KEITELMAN; A TREVANI; M GUZMÁN; M PALERMO

Mar del Plata

Congreso; LXVI Reunión Anual de la SAI/SAIC/SAFIS; 2018

SAI

Human Neutrophilssecrete IL-1β upon infection with Enterohemorrhagic Escherichia coliCarolina Maiumi Shiromizu1, Florencia Sabbione1,Irene Keitelman1, María Victoria Ramos1, MaximilianoMiglio1, Mauricio Guzmán1, Jeremías Galletti1,Carolina Jancic1, Marina Palermo1, Analía Trevani1,21 IMEX-CONICET-Academia Nacionalde Medicina; 2 Departamento de Microbiología,Parasitología e Inmunología, Facultad de Medicina, Universidad de Buenos Aires,Buenos Aires, Argentina 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 arenon-invasive bacteria that colonize the intestine where they release Stx thatthen reaches the blood stream; an event that might be facilitated by damages inthe intestinal mucosa and promoted by inflammation. Given that neutrophils(PMN) are recruited to the intestine after the infection, our aim was todetermine if these cells can contribute to the local inflammation by secretingIL-1β. We employed PMN isolated from peripheral blood of healthy donors. Thesecells were infected with Stx-producer Ecoli O157:H7 (E coli Stx+)or with the Stx-non-producer bacteria (Ecoli Stx-) and 4hs later we determined IL-1β levels in thesupernatants by ELISA. PMNs secreted IL-1β in similar levels in response toboth 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 infected by E coli Stx- was not modulated by additionof Stx type 2 (Stx2; 0.1 μg/ml). In addition, there were no differences betweenthe levels of IL-1β secreted in response to the culture supernatants of bothstrains (n=2). In accordance to these observations, Stx2 was unable per se of inducing IL-1β secretion or ofmodulating the secretion induced by PAM3CSK4 (a TLR2/1 agonist)+ATP. Inconclusion, PMN secrete IL-1β in response to E coli O157:H7, but this property is neither dependent nor ismodulated by Stx. These findings suggest that PMN might contribute to thepathology by increasing the local inflammation throughthe secretion of IL-1β.