Phenotype and functions of natural killer cells in critically-ill septic patients.
RATIONALE: Natural killer cells, as a major source of interferon-γ, contribute to the amplification of the inflammatory response as well as to mortality during severe sepsis in animal models. OBJECTIVE: We studied the phenotype and functions of circulating NK cells in critically-ill septic patients....
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3516510?pdf=render |
| _version_ | 1830287726623064064 |
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| author | Jean-Marie Forel Laurent Chiche Guillemette Thomas Julien Mancini Catherine Farnarier Céline Cognet Christophe Guervilly Aurélie Daumas Frédéric Vély François Xéridat Eric Vivier Laurent Papazian |
| author_facet | Jean-Marie Forel Laurent Chiche Guillemette Thomas Julien Mancini Catherine Farnarier Céline Cognet Christophe Guervilly Aurélie Daumas Frédéric Vély François Xéridat Eric Vivier Laurent Papazian |
| author_sort | Jean-Marie Forel |
| collection | DOAJ |
| description | RATIONALE: Natural killer cells, as a major source of interferon-γ, contribute to the amplification of the inflammatory response as well as to mortality during severe sepsis in animal models. OBJECTIVE: We studied the phenotype and functions of circulating NK cells in critically-ill septic patients. METHODS: Blood samples were taken <48 hours after admission from 42 ICU patients with severe sepsis (n = 15) or septic shock (n = 14) (Sepsis group), non-septic SIRS (n = 13) (SIRS group), as well as 21 healthy controls. The immuno-phenotype and functions of NK cells were studied by flow cytometry. RESULTS: The absolute number of peripheral blood CD3-CD56(+) NK cells was similarly reduced in all groups of ICU patients, but with a normal percentage of NK cells. When NK cell cytotoxicity was evaluated with degranulation assays (CD107 expression), no difference was observed between Sepsis patients and healthy controls. Under antibody-dependent cell cytotoxicity (ADCC) conditions, SIRS patients exhibited increased CD107 surface expression on NK cells (62.9[61.3-70]%) compared to healthy controls (43.5[32.1-53.1]%) or Sepsis patients (49.2[37.3-62.9]%) (p = 0.002). Compared to healthy (10.2[6.3-13.1]%), reduced interferon-γ production by NK cells (K562 stimulation) was observed in Sepsis group (6.2[2.2-9.9]%, p<0.01), and especially in patients with septic shock. Conversely, SIRS patients exhibited increased interferon-γ production (42.9[30.1-54.7]%) compared to Sepsis patients (18.4[11.7-35.7]%, p<0.01) or healthy controls (26.8[19.3-44.9]%, p = 0.09) in ADCC condition. CONCLUSIONS: Extensive monitoring of the NK-cell phenotype and function in critically-ill septic patients revealed early decreased NK-cell function with impaired interferon-γ production. These results may aid future NK-based immuno-interventions. TRIAL REGISTRATION: NTC00699868. |
| first_indexed | 2024-12-19T04:22:52Z |
| format | Article |
| id | doaj.art-13cc05370ca34cad87cebbdf8e24b58e |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T04:22:52Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-13cc05370ca34cad87cebbdf8e24b58e2022-12-21T20:36:06ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01712e5044610.1371/journal.pone.0050446Phenotype and functions of natural killer cells in critically-ill septic patients.Jean-Marie ForelLaurent ChicheGuillemette ThomasJulien ManciniCatherine FarnarierCéline CognetChristophe GuervillyAurélie DaumasFrédéric VélyFrançois XéridatEric VivierLaurent PapazianRATIONALE: Natural killer cells, as a major source of interferon-γ, contribute to the amplification of the inflammatory response as well as to mortality during severe sepsis in animal models. OBJECTIVE: We studied the phenotype and functions of circulating NK cells in critically-ill septic patients. METHODS: Blood samples were taken <48 hours after admission from 42 ICU patients with severe sepsis (n = 15) or septic shock (n = 14) (Sepsis group), non-septic SIRS (n = 13) (SIRS group), as well as 21 healthy controls. The immuno-phenotype and functions of NK cells were studied by flow cytometry. RESULTS: The absolute number of peripheral blood CD3-CD56(+) NK cells was similarly reduced in all groups of ICU patients, but with a normal percentage of NK cells. When NK cell cytotoxicity was evaluated with degranulation assays (CD107 expression), no difference was observed between Sepsis patients and healthy controls. Under antibody-dependent cell cytotoxicity (ADCC) conditions, SIRS patients exhibited increased CD107 surface expression on NK cells (62.9[61.3-70]%) compared to healthy controls (43.5[32.1-53.1]%) or Sepsis patients (49.2[37.3-62.9]%) (p = 0.002). Compared to healthy (10.2[6.3-13.1]%), reduced interferon-γ production by NK cells (K562 stimulation) was observed in Sepsis group (6.2[2.2-9.9]%, p<0.01), and especially in patients with septic shock. Conversely, SIRS patients exhibited increased interferon-γ production (42.9[30.1-54.7]%) compared to Sepsis patients (18.4[11.7-35.7]%, p<0.01) or healthy controls (26.8[19.3-44.9]%, p = 0.09) in ADCC condition. CONCLUSIONS: Extensive monitoring of the NK-cell phenotype and function in critically-ill septic patients revealed early decreased NK-cell function with impaired interferon-γ production. These results may aid future NK-based immuno-interventions. TRIAL REGISTRATION: NTC00699868.http://europepmc.org/articles/PMC3516510?pdf=render |
| spellingShingle | Jean-Marie Forel Laurent Chiche Guillemette Thomas Julien Mancini Catherine Farnarier Céline Cognet Christophe Guervilly Aurélie Daumas Frédéric Vély François Xéridat Eric Vivier Laurent Papazian Phenotype and functions of natural killer cells in critically-ill septic patients. PLoS ONE |
| title | Phenotype and functions of natural killer cells in critically-ill septic patients. |
| title_full | Phenotype and functions of natural killer cells in critically-ill septic patients. |
| title_fullStr | Phenotype and functions of natural killer cells in critically-ill septic patients. |
| title_full_unstemmed | Phenotype and functions of natural killer cells in critically-ill septic patients. |
| title_short | Phenotype and functions of natural killer cells in critically-ill septic patients. |
| title_sort | phenotype and functions of natural killer cells in critically ill septic patients |
| url | http://europepmc.org/articles/PMC3516510?pdf=render |
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