Early changes of CD4-positive lymphocytes and NK cells in patients with severe Gram-negative sepsis

Giamarellos‐Bourboulis, Evangelos J.; Τσαγανός, Θωμάς; Spyridaki, Ekaterini; Mouktaroudi, Maria; Plachouras, Diamantis; Vaki, Ilia; Karagianni, Vassiliki; Antonopoulou, Anastasia; Veloni, Vassiliki; Giamarellou, Helen

doi:10.1186/cc5111

Cited by 70 publications

(43 citation statements)

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“…We observed that NK lymphopenia was reported in most previous studies and it is hypothesized that NK cells migrate from the blood to inflamed tissue [31]. This NK lymphopenia was part of a global lymphopenia that involved B and T lymphocytes, which was more severe among septic patients and among non-survivors within the overall ICU population, as has been already reported [19], [31]. Conversely, and in agreement with the results of de Pablo et al [39], we could not observe any correlation between the numbers of circulating NK cells on admission and ICU mortality (even in the septic patients), as recently reported in a recent study [18].…”

Section: Discussionsupporting

confidence: 80%

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

et al. 2012

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RationaleNatural 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.ObjectiveWe studied the phenotype and functions of circulating NK cells in critically-ill septic patients.MethodsBlood 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.ResultsThe 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.ConclusionsExtensive 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 RegistrationNTC00699868.

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Section: Discussionsupporting

confidence: 80%

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

et al. 2012

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“…This decrease is the reflection of a general lymphopenia and may be due to the trafficking of NK cells to the sites of infection [46], or to apoptosis [47]. Interestingly, some reports suggest that NK cell percentages or counts are associated with outcome [48]. Our work further establishes that the decrease is similarly observed for both CD56 bright and CD56 dim NK cells subsets.…”

Section: Discussionsupporting

confidence: 72%

Toll-like receptors expression and interferon-γ production by NK cells in human sepsis

Souza-Fonseca-Guimarães

et al. 2012

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IntroductionDuring the course of infection, natural killer (NK) cells contribute to innate immunity by producing cytokines, particularly interferon-gamma (IFN-γ). In addition to their beneficial effects against infection, NK cells may play a detrimental role during systemic inflammation, causing lethality during sepsis. Little is known on the immune status of NK cells in patients with systemic inflammatory response syndrome (SIRS) or sepsis in terms of cell surface markers expression and IFN-γ production.MethodsWe investigated 27 sepsis patients and 11 patients with non-infectious SIRS. CD56bright and CD56dim NK cell subsets were identified by flow cytometry and Toll-like receptor (TLR)2, TLR4, TLR9, CX3CR1, CD16 and CD69 expression were analyzed, as well as ex vivo IFN-γ production by NK cells in whole blood samples.ResultsWe first showed that in NK cells from healthy controls, TLR2 and TLR4 expression is mainly intracellular, similarly to TLR9. Intracellular levels of TLR2 and TLR4, in both CD56bright and CD56dim NK cell subsets from sepsis patients, were increased compared to healthy subjects. In addition, the percentage of CD69+ cells was higher among NK cells of sepsis patients. No difference was observed for TLR9, CX3CR1, and CD16 expression. The ex vivo stimulation by TLR4 or TLR9 agonists, or whole bacteria in synergy with accessory cytokines (IL-15+IL-18), resulted in significant production of IFN-γ by NK cells of healthy controls. In contrast, for SIRS and sepsis patients this response was dramatically reduced.ConclusionsThis study reports for the first time an intracellular expression of TLR2 and TLR4 in human NK cells. Surface TLR4 expression allows discriminating sepsis and SIRS. Furthermore, during these pathologies, NK cells undergo an alteration of their immune status characterized by a profound reduction of their capacity to release IFN-γ.

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“…These facts explain why this cell subset has not been heavily investigated in sepsis 94,95 . Studies indicate that both CD56 hi and CD56 low NK cell subsets are affected during sepsis; the number of circulating NK cells is markedly decreased in septic patients 96,97 , which frequently persists for weeks 98 and is associated with increased mortality 99 . Furthermore, the absolute number of both NK cell subsets is decreased in sepsis 100 .…”

Section: Impact Of Sepsis On Immune Cellsmentioning

confidence: 99%

Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy

2013

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Sepsis — severe life-threatening infection with organ dysfunction — initiates a complex interplay of host pro- and anti-inflammatory processes. In a real sense, sepsis can be considered a race to the death between the pathogens and the host immune system. It is the proper balance between the often competing pro- and anti-inflammatory pathways that determines the fate of the individual. Although the field of sepsis research has witnessed the failure of many highly-touted clinical trials, a better understanding of the pathophysiological basis of the disorder and the mechanisms responsible for the associated pro- and anti-inflammatory responses is leading to a novel approach to treat this highly lethal condition. Biomarker-guided immunotherapy administered to patients at the proper immune phase of sepsis represents a potential major advance in the treatment of sepsis and more broadly in the field of infectious disease.

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Early changes of CD4-positive lymphocytes and NK cells in patients with severe Gram-negative sepsis

Abstract: Introduction Our aim was to define early changes of lymphocytes and of NK cells in severe sepsis and to correlate them with serum levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1).

Cited by 70 publications

References 20 publications

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

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

Toll-like receptors expression and interferon-γ production by NK cells in human sepsis

Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy

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