title: Upregulation of the inhibitory receptor ILT4 in monocytes from septic patients.
abstract: Sepsis-induced immune dysfunction is a complex phenomenon that involves both innate and adaptive responses. Upregulation of the inhibitor receptor named immunoglobulin like transcript 4 (ILT4) is crucial to the tolerogenic function of monocytes. Here, ILT4 expression, endotoxin-induced IL-12 and IL-10 production and CD86 expression were investigated in circulating monocytes from 16 patients with severe sepsis and 16 age and sex matched controls. We found that monocytes from patients with severe sepsis express significantly higher levels of ILT4 than monocytes from controls. Upregulation of ILT4 expression appeared to be induced by soluble factors present in the serum of septic patients and directly correlated with the degree of organ dysfunction. ILT4(+) monocytes from septic patients also displayed an alteration in the cytokine response to endotoxin stimulation characterized by reduced IL-12 production and increased IL-10 production, and a reduced expression of the costimulatory molecule CD86. In conclusion, the increased ILT4 expression and IL-10 production and the decreased CD86 expression and IL-12 production indicate that during sepsis monocytes undergo substantial modulation of the surface and cytokine phenotype. These phenotypic changes may interfere with the antigen presenting cell activity of monocytes, which may contribute to the impairment of adaptive immune responses that takes place during sepsis.
authors.affiliation: Dept. of Internal Medicine, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Baffari
authors.forename: Diego
authors.initials: D
authors.lastname: Fiume
authors.forename: Giordana
authors.initials: G
authors.lastname: Caiazzo
authors.forename: Anna
authors.initials: A
authors.lastname: Sinistro
authors.forename: Silvia
authors.initials: S
authors.lastname: Natoli
authors.forename: Cristiana
authors.initials: C
authors.lastname: Almerighi
authors.forename: Francesca
authors.initials: F
authors.lastname: Calò-Carducci
authors.forename: Francesca
authors.initials: F
authors.lastname: Leonardis
authors.forename: Alberto
authors.initials: A
authors.lastname: Bergamini
mesh_terms: D000368:Aged; D051940:B7-2 Antigen / Q000378:metabolism; D016022:Case-Control Studies; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D018805:Sepsis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D051940:B7-2 Antigen; D016207:Cytokines; C491341:LILRB2 protein, human; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic
keywords: APC; FITC; ILT4; LPS; PBMC; PC5; PE; R-phycoerythrin-cyanine; SAPS II; SOFA; Sequential Organ Failure Assessment score; Simplified Acute Physiology score; antigen presenting cell; fluorescein isothiocyanate; immunoglobulin like transcript 4; lipopolysaccharide; peripheral blood mononuclear cells; phycoerythrin