title: Marked alterations of neutrophil functions during sepsis-induced immunosuppression.
abstract: Severe septic syndromes deeply impair innate and adaptive immunity and are responsible for sepsis-induced immunosuppression. Although neutrophils represent the first line of defense against infection, little is known about their phenotype and functions a few days after sepsis, when the immunosuppressive phase is maximal (i.e., between d 3 and 8). The objective of the present study was to perform, for the first time, a global evaluation of neutrophil alterations in immunosuppressed septic patients (at d 3-4 and d 6-8) using phenotypic and functional studies. In addition, the potential association of these parameters and deleterious outcomes was assessed. Peripheral blood was collected from 43 septic shock patients and compared with that of 23 healthy controls. In the septic patients, our results highlight a markedly altered neutrophil chemotaxis (functional and chemokine receptor expressions), oxidative burst, and lactoferrin content and an increased number of circulating immature granulocytes (i.e., CD10(dim)CD16(dim)). These aspects were associated with an increased risk of death after septic shock. In contrast, phagocytosis and activation capacities were conserved. To conclude, circulating neutrophils present with phenotypic, functional, and morphologic alterations a few days after sepsis onset. These dysfunctions might participate in the deleterious role of sepsis-induced immunosuppression. The present results open new perspectives in the mechanisms favoring nosocomial infections after septic shock. They deserve to be further investigated in a larger clinical study and in animal models recapitulating these alterations.
authors.affiliation: Immunology Laboratory, bioMérieux Joint Research Unit, Hematology Laboratory, and Intensive Care Units, E. Herriot Hospital, Hospices Civils de Lyon, Lyon, France; University Claude Bernard Lyon 1, Lyon, France; and Intensive Care Units, Lyon-Sud Hospital, Hospices Civils de Lyon, Pierre-Bénite, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Demaret
authors.affiliation: Immunology Laboratory, bioMérieux Joint Research Unit, Hematology Laboratory, and Intensive Care Units, E. Herriot Hospital, Hospices Civils de Lyon, Lyon, France; University Claude Bernard Lyon 1, Lyon, France; and Intensive Care Units, Lyon-Sud Hospital, Hospices Civils de Lyon, Pierre-Bénite, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Venet
authors.affiliation: Immunology Laboratory, bioMérieux Joint Research Unit, Hematology Laboratory, and Intensive Care Units, E. Herriot Hospital, Hospices Civils de Lyon, Lyon, France; University Claude Bernard Lyon 1, Lyon, France; and Intensive Care Units, Lyon-Sud Hospital, Hospices Civils de Lyon, Pierre-Bénite, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Friggeri
authors.affiliation: Immunology Laboratory, bioMérieux Joint Research Unit, Hematology Laboratory, and Intensive Care Units, E. Herriot Hospital, Hospices Civils de Lyon, Lyon, France; University Claude Bernard Lyon 1, Lyon, France; and Intensive Care Units, Lyon-Sud Hospital, Hospices Civils de Lyon, Pierre-Bénite, France.
authors.forename: Marie-Angélique
authors.initials: MA
authors.lastname: Cazalis
authors.affiliation: Immunology Laboratory, bioMérieux Joint Research Unit, Hematology Laboratory, and Intensive Care Units, E. Herriot Hospital, Hospices Civils de Lyon, Lyon, France; University Claude Bernard Lyon 1, Lyon, France; and Intensive Care Units, Lyon-Sud Hospital, Hospices Civils de Lyon, Pierre-Bénite, France.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Plassais
authors.affiliation: Immunology Laboratory, bioMérieux Joint Research Unit, Hematology Laboratory, and Intensive Care Units, E. Herriot Hospital, Hospices Civils de Lyon, Lyon, France; University Claude Bernard Lyon 1, Lyon, France; and Intensive Care Units, Lyon-Sud Hospital, Hospices Civils de Lyon, Pierre-Bénite, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Jallades
authors.affiliation: Immunology Laboratory, bioMérieux Joint Research Unit, Hematology Laboratory, and Intensive Care Units, E. Herriot Hospital, Hospices Civils de Lyon, Lyon, France; University Claude Bernard Lyon 1, Lyon, France; and Intensive Care Units, Lyon-Sud Hospital, Hospices Civils de Lyon, Pierre-Bénite, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Malcus
authors.affiliation: Immunology Laboratory, bioMérieux Joint Research Unit, Hematology Laboratory, and Intensive Care Units, E. Herriot Hospital, Hospices Civils de Lyon, Lyon, France; University Claude Bernard Lyon 1, Lyon, France; and Intensive Care Units, Lyon-Sud Hospital, Hospices Civils de Lyon, Pierre-Bénite, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Poitevin-Later
authors.affiliation: Immunology Laboratory, bioMérieux Joint Research Unit, Hematology Laboratory, and Intensive Care Units, E. Herriot Hospital, Hospices Civils de Lyon, Lyon, France; University Claude Bernard Lyon 1, Lyon, France; and Intensive Care Units, Lyon-Sud Hospital, Hospices Civils de Lyon, Pierre-Bénite, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Textoris
authors.affiliation: Immunology Laboratory, bioMérieux Joint Research Unit, Hematology Laboratory, and Intensive Care Units, E. Herriot Hospital, Hospices Civils de Lyon, Lyon, France; University Claude Bernard Lyon 1, Lyon, France; and Intensive Care Units, Lyon-Sud Hospital, Hospices Civils de Lyon, Pierre-Bénite, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Lepape
authors.affiliation: Immunology Laboratory, bioMérieux Joint Research Unit, Hematology Laboratory, and Intensive Care Units, E. Herriot Hospital, Hospices Civils de Lyon, Lyon, France; University Claude Bernard Lyon 1, Lyon, France; and Intensive Care Units, Lyon-Sud Hospital, Hospices Civils de Lyon, Pierre-Bénite, France guillaume.monneret@chu-lyon.fr.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Monneret
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005500:Follow-Up Studies; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D008297:Male; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D019707:Receptors, Chemokine / Q000097:blood / Q000276:immunology*; D018805:Sepsis / Q000097:blood / Q000276:immunology* / Q000473:pathology; D013997:Time Factors
chemical_list: D019707:Receptors, Chemokine
keywords: CD10; CD16; myeloperoxidase; septic shock