Phenotype and Functions of Natural Killer Cells in Critically-Ill Septic Patients

Forel, Jean-Marie; Chiche, Laurent; Thomas, G.; Mancini, Julien; Farnarier, Catherine; Cognet, Céline; Guervilly, Christophe; Daumas, Aurélie; Vély, Frederic; Xeridat, F.; Vivier, Éric; Papazian, Laurent

doi:10.1371/journal.pone.0050446

Cited by 70 publications

(72 citation statements)

References 47 publications

(64 reference statements)

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“…NK cells are a major source of interferon-g (IFN-g), a potent inflammatory cytokine, and early depletion of NK cells improved survival in sepsis models in the mouse. 36,37 We also recently observed that both NK-cell cytotoxicity and IFN-g production were decreased in sepsis, 38 consistent with similar results obtained in mice. 39 Considering the sequence of opposite events that are at work during sepsis, NK cells might have a dual role in sepsis, first contributing to the amplification of the inflammatory response during the early steps of SIRS and then, impaired during CARS and thus participating to its detrimental consequences.…”

Section: Discussionsupporting

confidence: 88%

“…39 Considering the sequence of opposite events that are at work during sepsis, NK cells might have a dual role in sepsis, first contributing to the amplification of the inflammatory response during the early steps of SIRS and then, impaired during CARS and thus participating to its detrimental consequences. 38,40,41 Our data on B7-H6 expression during inflammation provide a novel perspective on the link between microbial infection and NK-cell activation. First, B7-H6 was selectively induced on the surface of CD14…”

Section: Discussionmentioning

confidence: 88%

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Induction of B7-H6, a ligand for the natural killer cell–activating receptor NKp30, in inflammatory conditions

Matta

Baratin

Chiche

et al. 2013

Blood

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120

128

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• B7-H6 transcripts, B7-H6 cell-surface expression, and sB7-H6 can be induced in inflammatory conditions in vitro and in vivo.• B7-H6 is expressed on proinflammatory CD141 CD16 1 monocytes in sepsis conditions and is linked to an increased mortality.B7-H6, a member of the B7 family of immunoreceptors, is as a cell-surface ligand for the NKp30-activating receptor expressed on natural killer cells. B7-H6 is not detected in normal human tissues at steady state but is expressed on tumor cells. However, whether B7-H6 can be expressed in other conditions remains unknown. We analyzed here the pathways that lead to the expression of B7-H6 in nontransformed cells. In vitro, B7-H6 was induced at the surface of CD14 1 CD16 1 proinflammatory monocytes and neutrophils upon stimulation by ligands of Toll-like receptors or proinflammatory cytokines such as interleukin-1b and tumor necrosis factor a. In these conditions, a soluble form of B7-H6 (sB7-H6) was also produced by activated monocytes and neutrophils. In vivo, B7-H6 was expressed on circulating proinflammatory CD14 1 CD16 1 monocytes in a group of patients in sepsis conditions, and was linked to an increased mortality. sB7-H6 was selectively detected in the sera of patients with gram-negative sepsis and was associated with membrane vesicles that co-sedimented with the exosomal fraction. These findings reveal that B7-H6 is not only implicated in tumor immunosurveillance but also participates in the inflammatory response in infectious conditions. This trial was registered at www.clinicaltrials.gov as #NTC00699868. (Blood. 2013;122(3):394-404)

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 88%

Induction of B7-H6, a ligand for the natural killer cell–activating receptor NKp30, in inflammatory conditions

Matta

Baratin

Chiche

et al. 2013

Blood

Self Cite

120

128

View full text Add to dashboard Cite

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“…Previous studies have revealed an early decrease of NK-cell function in patients with septic or severe TBI [15,16] .…”

Section: Introductionmentioning

confidence: 97%

Alterations of natural killer cells in traumatic brain injury

et al. 2014

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To investigate the relationship between natural killer (NK) cells and traumatic brain injury (TBI), we tracked an established phenotype of circulating NK cells at several time points in patients with different grades of TBI. In serial peripheral blood samples, NK cells were prospectively measured by flow cytometry of CD3(-) CD56(+) lymphocytes. Compared to healthy controls, TBI patients had reductions in both the percentage and the absolute number of NK cells. Furthermore, the magnitude of NK cell reduction correlated with the degree of TBI severity at several time points. That is, NK cell population size was independently associated with lower Glasgow Coma Scale scores. In addition, at some time points, a positive correlation was found between the NK cell counts and Glasgow Outcome Scale scores. Our results indicate that TBI induces a reduction in the number of NK cells, and the magnitude of the reduction appears to parallel the severity of TBI.

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“…Several studies have demonstrated considerable role for NKG2D in protective function against virus infected or transformed cells [5,37,45]. The liver lymphocyte population is enriched with NK cells and these cells are one of the main cell populations, expressing NKG2D [11,42]. The major NK cell functions include direct killing of target cells as well as cytokine production such as IFN-c [11].…”

Section: Nkg2d Polymorphism Effects On Peginterferon Alfa-2a/ribavirimentioning

confidence: 99%

“…The liver lymphocyte population is enriched with NK cells and these cells are one of the main cell populations, expressing NKG2D [11,42]. The major NK cell functions include direct killing of target cells as well as cytokine production such as IFN-c [11]. NKG2D ligation induces calcium flux, cytokine release, and cytotoxicity in NK cells.…”

Section: Nkg2d Polymorphism Effects On Peginterferon Alfa-2a/ribavirimentioning

confidence: 99%

Peginterferon Alfa-2a/Ribavirin treatment efficacy in chronic hepatitis C patients is related to natural killer group 2D gene rs1049174 GC polymorphism

et al. 2016

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Natural killer group 2D (NKG2D), as an activating receptor, plays pivotal role in viral infectious diseases. Several single nucleotide polymorphisms (SNPs) in the NKG2D gene have characterized that the rs1049174G/ C SNP of NKG2D is in the spotlight of notice because of its role in activating of human T cells. This study aimed to investigate rs1049174G/C genetic polymorphism in Chronic Hepatitis C (CHC) patients. The study compromised 107 CHC patients with genotype 1a and 1b. All recruited patients were under treatment with Peginterferon Alfa-2a/Ribavirin according to standard protocol. After completing treatment, 67 patients showed sustained virologic response (SVR) and the rest of patients did not respond to the treatment and considered as non-responder (NR). Genotyping of NKG2D rs1049174G/C SNP was performed using PCR-RFLP method in SVR and NR patients. The NKG2D rs1049174 genotypes frequency for GG, GC and CC were 45, 41 and 14 % respectively. Genotypes distribution were significantly different between SVR and NR groups (p = 0.005). So that the patients with the homozygous GG genotype demonstrated a higher response to Peginterferon Alfa-2a/Ribavirin therapy against HCV infection (OR = 6.0, 95 %CI 1.71-21.08, p = 0.005). In conclusion, the rs1049174 GG genotype of NKG2D receptor is an effective factor in successfully treatment of CHC patients by Peginterferon Alfa-2a/ Ribavirin.

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Phenotype and Functions of Natural Killer Cells in Critically-Ill Septic Patients

Cited by 70 publications

References 47 publications

Induction of B7-H6, a ligand for the natural killer cell–activating receptor NKp30, in inflammatory conditions

Induction of B7-H6, a ligand for the natural killer cell–activating receptor NKp30, in inflammatory conditions

Alterations of natural killer cells in traumatic brain injury

Peginterferon Alfa-2a/Ribavirin treatment efficacy in chronic hepatitis C patients is related to natural killer group 2D gene rs1049174 GC polymorphism

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