Marked alterations of neutrophil functions during sepsis-induced immunosuppression

被引:153
作者
Demaret, Julie [1 ,2 ]
Venet, Fabienne [1 ,2 ]
Friggeri, Arnaud [3 ]
Cazalis, Marie-Angelique [4 ]
Plassais, Jonathan [4 ]
Jallades, Laurent [5 ]
Malcus, Christophe [1 ]
Poitevin-Later, Francoise [1 ]
Textoris, Julien [4 ,6 ]
Lepape, Alain [3 ]
Monneret, Guillaume [1 ,2 ]
机构
[1] Hosp Civils Lyon, E Herriot Hosp, Immunol Lab, F-69437 Lyon 03, France
[2] Hosp Civils Lyon, E Herriot Hosp, BioMerieux Joint Res Unit, F-69437 Lyon 03, France
[3] Hosp Civils Lyon, E Herriot Hosp, Hematol Lab, F-69437 Lyon 03, France
[4] Hosp Civils Lyon, E Herriot Hosp, Intens Care Units, F-69437 Lyon 03, France
[5] Univ Lyon 1, F-69365 Lyon, France
[6] Hosp Civils Lyon, Lyon Sud Hosp, Intens Care Units, Pierre Benite, France
关键词
septic shock; CD10; CD16; myeloperoxidase; ORGAN FAILURE; EXPRESSION;
D O I
10.1189/jlb.4A0415-168RR
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:1081 / 1090
页数:10
相关论文
共 22 条
[1]   Neutrophil Function: From Mechanisms to Disease [J].
Amulic, Borko ;
Cazalet, Christel ;
Hayes, Garret L. ;
Metzler, Kathleen D. ;
Zychlinsky, Arturo .
ANNUAL REVIEW OF IMMUNOLOGY, VOL 30, 2012, 30 :459-489
[2]   DEFINITIONS FOR SEPSIS AND ORGAN FAILURE AND GUIDELINES FOR THE USE OF INNOVATIVE THERAPIES IN SEPSIS [J].
BONE, RC ;
BALK, RA ;
CERRA, FB ;
DELLINGER, RP ;
FEIN, AM ;
KNAUS, WA ;
SCHEIN, RMH ;
SIBBALD, WJ .
CHEST, 1992, 101 (06) :1644-1655
[3]   Neutrophils in development of multiple organ failure in sepsis [J].
Brown, K. A. ;
Brain, S. D. ;
D Pearson, J. ;
D Edgeworth, J. ;
Lewis, S. M. ;
Treacher, D. F. .
LANCET, 2006, 368 (9530) :157-169
[4]   Inter-laboratory assessment of flow cytometric monocyte HLA-DR expression in clinical samples [J].
Demaret, Julie ;
Walencik, Alexandre ;
Jacob, Marie-Christine ;
Timsit, Jean-Francois ;
Venet, Fabienne ;
Lepape, Alain ;
Monneret, Guillaume .
CYTOMETRY PART B-CLINICAL CYTOMETRY, 2013, 84B (01) :59-62
[5]   Innate Immune Functions of Immature Neutrophils in Patients With Sepsis and Severe Systemic Inflammatory Response Syndrome [J].
Drifte, Genevieve ;
Dunn-Siegrist, Irene ;
Tissieres, Pierre ;
Pugin, Jerome .
CRITICAL CARE MEDICINE, 2013, 41 (03) :820-832
[6]   Circulating Immature Granulocytes With T-Cell Killing Functions Predict Sepsis Deterioration [J].
Guerin, Estelle ;
Orabona, Marie ;
Raquil, Marie-Astrid ;
Giraudeau, Bruno ;
Bellier, Remy ;
Gibot, Sebastien ;
Bene, Marie-Christine ;
Lacombe, Francis ;
Droin, Nathalie ;
Solary, Eric ;
Vignon, Philippe ;
Feuillard, Jean ;
Francois, Bruno .
CRITICAL CARE MEDICINE, 2014, 42 (09) :2007-2018
[7]   Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy [J].
Hotchkiss, Richard S. ;
Monneret, Guillaume ;
Payen, Didier .
NATURE REVIEWS IMMUNOLOGY, 2013, 13 (12) :862-874
[8]   Immunosuppression in sepsis: a novel understanding of the disorder and a new therapeutic approach [J].
Hotchkiss, Richard S. ;
Monneret, Guillaume ;
Payen, Didier .
LANCET INFECTIOUS DISEASES, 2013, 13 (03) :260-268
[9]   Tilting toward immunosuppression [J].
Hotchkiss, Richard S. ;
Coopersmith, Craig M. ;
McDunn, Jonathan E. ;
Ferguson, Thomas A. .
NATURE MEDICINE, 2009, 15 (05) :496-497
[10]   The function of neutrophils in sepsis [J].
Kovach, Melissa A. ;
Standiford, Theodore J. .
CURRENT OPINION IN INFECTIOUS DISEASES, 2012, 25 (03) :321-327