Natural killer cell cytotoxicity is deficient in newborns with sepsis and recurrent infections

Georgeson, George D; Szóny, Barnabás József; Streitman, K; Kovács, Attila; Kovács, László; László, A

doi:10.1007/s004310100773

Cited by 48 publications

(33 citation statements)

References 24 publications

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“…Although similar findings regarding human neonatal/perinatal cells against human viruses and bacterias have been reported, 21,25 this is to our knowledge the first report indicating a defect of NK responses against replication-competent SeVs in neonatal mice. In addition, these results suggest that the lack of NK cell response against viruses may be ubiquitous in neonates of any mammalian species.…”

Section: Discussionsupporting

confidence: 83%

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Impact of deletion of envelope-related genes of recombinant Sendai viruses on immune responses following pulmonary gene transfer of neonatal mice

et al. 2007

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We demonstrated previously that the additive-type recombinant Sendai virus (rSeV) is highly efficient for use in pulmonary gene transfer; however, rSeV exhibits inflammatory responses. To overcome this problem, we tested newly developed non-transmissible constructs, namely, temperature-sensitive F-deleted vector, rSeV/dF (ts-rSeV/dF) and a rSeV with all the envelope-related genes deleted (rSeV/ dFdMdHN), for pulmonary gene transfer in neonatal mice, by assessing their toxicity and immune responses. The gene expression in the lungs of neonatal ICR mice peaked on day 2, then gradually decreased until almost disappearing at 14 days after infection in all constructs. Loss of body weight and mortality rate, however, were dramatically improved in mice treated with SeV/dFdMdHN (mortality ¼ 0%, n ¼ 41) and ts-rSeV/dF (24.2%, n ¼ 33) compared with additive rSeV (70.7%, n ¼ 58). Although the deletion of envelope-related genes of SeV had a small impact on the production of antibody and cytotoxic T-lymphocyte activity in both adults and neonates, a dramatic reduction was found in the events related to innate responses, including the production of proinflammatory cytokines, particularly in the case of neonates. These results indicate that pulmonary gene transfer using SeV/dFdMdHN warrants further investigation for its possible use in developing safer therapeutics for neonatal lung diseases, including cystic fibrosis.

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Section: Discussionsupporting

confidence: 83%

“…The loss of NK cell responses have also been demonstrated in the case of other organisms, including Candida albicans, Escherichia coli, Listeria monocytogenes, etc. 21 …”

Section: Lack Of Nk Cell Activity In Neonatal Micementioning

confidence: 99%

Impact of deletion of envelope-related genes of recombinant Sendai viruses on immune responses following pulmonary gene transfer of neonatal mice

et al. 2007

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“…According to the present results, no difference in cytotoxicity was observed between MPB and CB samples, in contrast to studies that reported suppression of NK cell cytotoxicity in postpartum women [48]. The same suppression pattern was observed in NK cells from premature infants, as compared to those from full-term infants [49][50][51], indicating that not only the number, but also the function differs according to the type of delivery. The standard method for determining NK activity is the chromium-release assay; however, this assay is not a preferred method for use in clinical laboratories for a variety of reasons, e.g.…”

Section: Akdeniz Et Al Differences In Cord Bloodcontrasting

confidence: 78%

Differences in lymphocyte subpopulation count and function in cord, maternal and adult blood

Akdeniz¹,

Aktaş²,

Erten³

et al. 2011

Turk J Hematol

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Objective: Phenotypical characterization and functional activity of lymphocytes and natural killer (NK) cells in cord blood (CB) were investigated, and maternal peripheral blood (MPB) values were compared to those of adult peripheral blood (APB) (control). Materials and Methods: To determine cytotoxic activity target cells (K562) were labeled with carboxyfluorescein diacetate (CFDA) or fluorescein isothiocyanate (FITC), and propidium iodide (PI) was used to label dead cells. Cell surface expression in CB, APB, and MPB cells were analyzed using flow cytometry. Results: CB and MPB mononuclear cells had similar CD45, CD34, CD4, and surface molecule for T helper cell expression, but had low-level expression of total T-lymphocyte surface molecules CD3 and CD8. CD19 and HLA-DR expression was higher in CB than in MPB. The same high-level of expression for CD19 and HLA-DR was observed in APB, as compared to MPB. All other cell surface expressions were similar in APB and MPB samples. NK (CD16 + and CD56 + ) cells in CB was similar to that in MPB and APB, and the level of inhibitory KIR receptors in NK cells was higher in venous CB than in MPB and APB. The only difference between MPB and APB was that the CD158a level was higher in MPB. No difference was observed in NK cells in CB and MPB, in terms of cytotoxicity. Conclusion: The present results show that there was numerical and proportional variability of lymphocytes and their subgroups in CB and APB, but no cytological difference. (Turk J Hematol 2011; 28: 33-41) Key words: NK activity, cord blood lymphocytes, flow cytometry

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“…Immune status of NK cells is also affected during sepsis. NK cells' cytotoxic activity in adult and newborn sepsis patients is decreased (23,39,40). Similar observations were reproduced in animal models after surgery, peritonitis, or injection of LPS or other TLR agonists (41)(42)(43).…”

Section: Discussionmentioning

confidence: 60%

NK Cell Tolerance to TLR Agonists Mediated by Regulatory T Cells after Polymicrobial Sepsis

Souza-Fonseca-Guimarães

Parlato

Fitting

et al. 2012

The Journal of Immunology

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As sensors of infection, innate immune cells are able to recognize pathogen-associated molecular patterns by receptors such as TLRs. NK cells present in many tissues contribute to inflammatory processes, particularly through the production of IFN-γ. They may display a protective role during infection but also a detrimental role during sterile or infectious systemic inflammatory response syndrome. Nevertheless, the exact status of NK cells during bacterial sepsis and their capacity directly to respond to TLR agonists remain unclear. The expression of TLRs in NK cells has been widely studied by analyzing the mRNA of these receptors. The aim of this study was to gain insight into TLR2/TLR4/TLR9 expression on/in murine NK cells at the protein level and determine if their agonists were able to induce cytokine production. We show, by flow cytometry, a strong intracellular expression of TLR2 and a low of TLR4 in freshly isolated murine spleen NK cells, similar to that of TLR9. In vitro, purified NK cells respond to TLR2, TLR4, and TLR9 agonists, in synergy with activating cytokines (IL-2, IL-15, and/or IL-18), and produce proinflammatory cytokines (IFN-γ and GM-CSF). Finally, we explored the possible tolerance of NK cells to TLR agonists after a polymicrobial sepsis (experimental peritonitis). For the first time, to our knowledge, NK cells are shown to become tolerant in terms of proinflammatory cytokines production after sepsis. We show that this tolerance is associated with a reduction of the CD27+CD11b− subset in the spleen related to the presence of regulatory T cells and mainly mediated by TGF-β.

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Natural killer cell cytotoxicity is deficient in newborns with sepsis and recurrent infections

Abstract: Natural killer cell cytotoxicity is deficient in both neonatal sepsis and recurrent infections.

Cited by 48 publications

References 24 publications

Impact of deletion of envelope-related genes of recombinant Sendai viruses on immune responses following pulmonary gene transfer of neonatal mice

Impact of deletion of envelope-related genes of recombinant Sendai viruses on immune responses following pulmonary gene transfer of neonatal mice

Differences in lymphocyte subpopulation count and function in cord, maternal and adult blood

NK Cell Tolerance to TLR Agonists Mediated by Regulatory T Cells after Polymicrobial Sepsis

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