Modulation of LILRB2 protein and mRNA expressions in septic shock patients and after ex vivo lipopolysaccharide stimulation.
Septic patients develop immune dysfunctions, the intensities and durations of which are associated with deleterious outcomes. LILRB2 (leukocyte immunoglobulin-like receptors subfamily B, member 2), an inhibitory member of the LILR family of receptors, is known for its immunoregulatory properties. In a microarray study, we identified LILRB2 as an upregulated gene in septic shock patients. On monocytes primed with LPS ex vivo, LILRB2 mRNA and protein expressions were dose-dependently downregulated and subsequently highly upregulated versus non-stimulated cells. This is concordant with clinical data, since both LILRB2 mRNA and protein expressions were significantly increased in septic shock patients at day 3. In a cohort of more than 700 patients, only after septic shock were LILRB2 mRNA levels increased compared with non-infected or less severely infected patients. This was preceded by a phase of downregulated mRNA expression during the first hours after septic shock. Interestingly, the intensity of this decrease was associated with increased risk of death after septic shock. LILRB2 protein and mRNA expressions are deregulated on monocytes after septic shock and this can be reproduced ex vivo after LPS challenge. Considering LILRB2 inhibitory properties, we can hypothesize that LILRB2 may participate in the altered immune response after septic shock.
Hospices Civils de Lyon, Immunology Laboratory, Groupement Hospitalier Edouard Herriot, Lyon, France; EA 7426 Hospices Civils de Lyon - bioMérieux - UCBL1 "Pathophysiology of Injury-induced Immunosuppression", Joint Research Unit, Groupement Hospitalier Edouard Herriot, Lyon, France. Electronic address: fabienne.venet@chu-lyon.fr.
Fabienne
F
Venet
EA 7426 Hospices Civils de Lyon - bioMérieux - UCBL1 "Pathophysiology of Injury-induced Immunosuppression", Joint Research Unit, Groupement Hospitalier Edouard Herriot, Lyon, France.
Jeremy
J
Schilling
EA 7426 Hospices Civils de Lyon - bioMérieux - UCBL1 "Pathophysiology of Injury-induced Immunosuppression", Joint Research Unit, Groupement Hospitalier Edouard Herriot, Lyon, France.
Marie-Angélique
MA
Cazalis
Hospices Civils de Lyon, Immunology Laboratory, Groupement Hospitalier Edouard Herriot, Lyon, France; EA 7426 Hospices Civils de Lyon - bioMérieux - UCBL1 "Pathophysiology of Injury-induced Immunosuppression", Joint Research Unit, Groupement Hospitalier Edouard Herriot, Lyon, France.
Julie
J
Demaret
EA 7426 Hospices Civils de Lyon - bioMérieux - UCBL1 "Pathophysiology of Injury-induced Immunosuppression", Joint Research Unit, Groupement Hospitalier Edouard Herriot, Lyon, France.
Fanny
F
Poujol
EA 7426 Hospices Civils de Lyon - bioMérieux - UCBL1 "Pathophysiology of Injury-induced Immunosuppression", Joint Research Unit, Groupement Hospitalier Edouard Herriot, Lyon, France; Hospices Civils de Lyon, Anesthesiology and Critical Care Medicine Department, Groupement Hospitalier Edouard Herriot, University Claude Bernard Lyon 1, Lyon, France.
Thibaut
T
Girardot
EA 7426 Hospices Civils de Lyon - bioMérieux - UCBL1 "Pathophysiology of Injury-induced Immunosuppression", Joint Research Unit, Groupement Hospitalier Edouard Herriot, Lyon, France; Hospices Civils de Lyon, Anesthesiology and Critical Care Medicine Department, Groupement Hospitalier Edouard Herriot, University Claude Bernard Lyon 1, Lyon, France.
Christelle
C
Rouget
EA 7426 Hospices Civils de Lyon - bioMérieux - UCBL1 "Pathophysiology of Injury-induced Immunosuppression", Joint Research Unit, Groupement Hospitalier Edouard Herriot, Lyon, France.
Alexandre
A
Pachot
Hospices Civils de Lyon, Intensive Care Unit, Centre Hospitalier Lyon Sud, Pierre Bénite, France.
Alain
A
Lepape
Hospices Civils de Lyon, Intensive Care Unit, Centre Hospitalier Lyon Sud, Pierre Bénite, France.
Arnaud
A
Friggeri
EA 7426 Hospices Civils de Lyon - bioMérieux - UCBL1 "Pathophysiology of Injury-induced Immunosuppression", Joint Research Unit, Groupement Hospitalier Edouard Herriot, Lyon, France; Hospices Civils de Lyon, Anesthesiology and Critical Care Medicine Department, Groupement Hospitalier Edouard Herriot, University Claude Bernard Lyon 1, Lyon, France.
Thomas
T
Rimmelé
Hospices Civils de Lyon, Immunology Laboratory, Groupement Hospitalier Edouard Herriot, Lyon, France; EA 7426 Hospices Civils de Lyon - bioMérieux - UCBL1 "Pathophysiology of Injury-induced Immunosuppression", Joint Research Unit, Groupement Hospitalier Edouard Herriot, Lyon, France.
Guillaume
G
Monneret
EA 7426 Hospices Civils de Lyon - bioMérieux - UCBL1 "Pathophysiology of Injury-induced Immunosuppression", Joint Research Unit, Groupement Hospitalier Edouard Herriot, Lyon, France; Hospices Civils de Lyon, Anesthesiology and Critical Care Medicine Department, Groupement Hospitalier Edouard Herriot, University Claude Bernard Lyon 1, Lyon, France.
Julien
J
Textoris
D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D015331:Cohort Studies; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D056747:Immunomodulation; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics*; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D012306:Risk; D012772:Shock, Septic / Q000276:immunology* / Q000401:mortality; D016019:Survival Analysis
C491341:LILRB2 protein, human; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic
Leukocyte immunoglobulin-like receptors 2; Monocyte; Mortality; Neutrophil; Sepsis