Phagosomal granulocytic ROS in septic patients induce the bacterial SOS response
Stecy Chollet,
Ana Catalina Hernandez Padilla,
Thomas Daix,
Margaux Gaschet,
Bruno François,
Christophe Piguet,
Nathalie Gachard,
Sandra Da Re,
Robin Jeannet,
Marie-Cécile Ploy
Affiliations
Stecy Chollet
University Limoges, Inserm, CHU Limoges, RESINFIT, U 1092, F-87000 Limoges, France
Ana Catalina Hernandez Padilla
University Limoges, Inserm, CHU Limoges, RESINFIT, U 1092, F-87000 Limoges, France
Thomas Daix
University Limoges, Inserm, CHU Limoges, RESINFIT, U 1092, F-87000 Limoges, France; CHU Limoges, Service de Réanimation Polyvalente, Limoges, France; Inserm CIC 1435, Limoges, France
Margaux Gaschet
University Limoges, Inserm, CHU Limoges, RESINFIT, U 1092, F-87000 Limoges, France
Bruno François
University Limoges, Inserm, CHU Limoges, RESINFIT, U 1092, F-87000 Limoges, France; CHU Limoges, Service de Réanimation Polyvalente, Limoges, France; Inserm CIC 1435, Limoges, France
Christophe Piguet
CHU Limoges, Département de pédiatrie médicale, Limoges, France
Nathalie Gachard
CHU Limoges, Laboratoire d’hématologie, Limoges, France; CNRS UMR 7276, Inserm UMR 1262, Université de Limoges, Limoges, France
Sandra Da Re
University Limoges, Inserm, CHU Limoges, RESINFIT, U 1092, F-87000 Limoges, France
Robin Jeannet
Inserm CIC 1435, Limoges, France; CNRS UMR 7276, Inserm UMR 1262, Université de Limoges, Limoges, France; Corresponding author
Marie-Cécile Ploy
University Limoges, Inserm, CHU Limoges, RESINFIT, U 1092, F-87000 Limoges, France
Summary: Septic patients with worst clinical prognosis have increased circulating immature granulocytes (IG), displaying limited phagocytosis and reactive oxygen species (ROS) production. Here, we developed an ex vivo model of incubation of human granulocytes, from septic patients or healthy donors, with Escherichia coli. We showed that the ROS production in Sepsis-IG is lower due to decreased activation and protein expression of the NADPH oxidase complex. We also demonstrated that the low level of ROS production and lower phagocytosis of IG in sepsis induce the bacterial SOS response, leading to the expression of the SOS-regulated quinolone resistance gene qnrB2. Without antimicrobial pressure, the sepsis immune response alone may promote antibiotic resistance expression.