EZH2 identifies the precursors of human natural killer cells with trained immunity

Zhang, Chen; Yin, Jie; Zheng, Jian; Xiao, Jun; Hu, Jiajian; Su, Yuxi; Zhou, Kaichen; Zhang, Yingchi; Zhang, Xuzhen; Zhang, Hong; Sun, Qian; Wang, Yang; Yu, Wenwen; Wei, Feng; Zhao, Qiang; Li, Long; Ren, Xiubao

doi:10.20892/j.issn.2095-3941.2020.0791

Cited by 8 publications

(5 citation statements)

References 25 publications

(36 reference statements)

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“…In addition, there was also BCG activation of γδ T cells (IL4 and IL17) but lower compared to Macrophage activation (TNF α and IL10). However, limited activation was observed for NK cells (IL2) (16, 34). The redundancy in cytokine secretion from different sources makes it difficult to evaluate individual contribution of cell subtypes.…”

Section: Discussionmentioning

confidence: 99%

BCG activation of trained immunity is associated with induction of cross reactive COVID-19 antibodies in a BCG vaccinated population

Iqbal,

Ahmed,

Sattar

et al. 2024

Preprint

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BackgroundDuring the current COVID-19 pandemic, the rate of morbidity and mortality was considerably lower in BCG vaccinated countries like Pakistan. BCG has been shown to provide cross protection to both disseminated TB as well as non related viral infections in BCG vaccinated children which is consistent with COVID-19 morbidity in the younger age group. Recently, this cross protection was attributed to trained immunity (TI) associated with BCG recall responses in the innate arm of the immune system. Little is known about the longevity of BCG Trained Immunity (TI) beyond early childhood.ObjectiveTo assess the BCG-induced recall responses in healthy individuals by cytokines secreted from the TI network and its potential role in providing cross-protection against COVID-19 and other viral infections.Study DesignIn this cross-sectional study, healthy young adults and adolescents (n=20) were recruited from 16–40 years of age, with no prior history of TB treatment, autoimmune, or chronic inflammatory condition.MethodsBCG-induced cytokine responses were assessed using prototypic markers for cells of the TI network {macrophages [M1 (TNFα, IFNγ), M2 (IL10)], NK (IL2), Gamma delta (γδ) T (IL17, IL4)} and SARS CoV2 IgG antibodies against RBD using short-term (12 hrs.) cultures assay.ResultsSignificant differences were observed in the magnitude of recall responses to BCG with macrophage cytokines showing the highest mean levels of TNFα (9148 pg/ml) followed by IL10 (488 pg/ml) and IFNγ (355 pg/ml). The ratio of unstimulated vs.BCG-stimulated cytokines was 132 fold higher for TNFα, 40 fold for IL10, and 27 fold for IFNγ. Furthermore, SARS-CoV-2 antibodies were also detected in unstimulated plasma which showed cross reactivity with BCG.ConclusionThe presence of cross reactive antibodies to SARS-CoV-2 and the relative ratio of pro-and anti-inflammatory cytokines secreted by activated TI cellular network may play a pivotal role in protection in the early stages of infection as observed during the COVID-19 pandemic in the younger age groups resulting in lower morbidity and mortality.

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Section: Discussionmentioning

confidence: 99%

BCG activation of trained immunity is associated with induction of cross reactive COVID-19 antibodies in a BCG vaccinated population

Iqbal,

Ahmed,

Sattar

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…In addition, there was also BCG activation of γδ T cells (IL4 and IL17) but lower compared to Macrophage activation (TNFα and IL10). However, limited activation was observed for NK cells (IL2) [ 16 , 35 ]. The redundancy in cytokine secretion from different sources makes it difficult to evaluate individual contribution of cell subtypes.…”

Section: Discussionmentioning

confidence: 99%

BCG activation of trained immunity is associated with induction of cross reactive COVID-19 antibodies in a BCG vaccinated population

Iqbal,

Ahmed,

Sattar

et al. 2024

PLoS ONE

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Background Pakistan is endemic to a diverse set of parasitic, mycobacterial and viral diseases. The recognition of BCG Trained Immunity (TI) led us to postulate that the continued presence of BCG-TI may play a protective role, previously reported for both infectious and noninfectious conditions. Most of the previous studies have addressed the issue of BCG-TI in the paediatric populations. This study addressed the key issue of maintenance of BCG-TI in a wider age range (adolescent and adults) to identify the strength and quality of the immune responses. Objective To assess the BCG-induced recall responses in healthy individuals by cytokines secreted from the TI network and its potential role in providing cross-protection against COVID-19 and other viral infections. Study design In this cross-sectional study, healthy young adults and adolescents (n = 20) were recruited from 16–40 years of age, with no prior history of TB treatment, autoimmune, or chronic inflammatory condition. Methods BCG-induced cytokine responses were assessed using prototypic markers for cells of the TI network [macrophages [M1 (TNFα, IFNγ), M2 (IL10)], NK (IL2), Gamma delta (γδ) T (IL17, IL4)] and SARS CoV2 IgG antibodies against RBD using short-term (12 hrs.) cultures assay. Results Significant differences were observed in the magnitude of recall responses to BCG with macrophage cytokines showing the highest mean levels of TNFα (9148 pg/ml) followed by IL10 (488 pg/ml) and IFNγ (355 pg/ml). The ratio of unstimulated vs.BCG-stimulated cytokines was 132 fold higher for TNFα, 40 fold fo r IL10, and 27 fold for IFNγ. Furthermore, SARS-CoV-2 antibodies were also detected in unstimulated plasma which showed cross reactivity with BCG. Conclusion The presence of cross reactive antibodies to SARS-CoV-2 and the relative ratio of pro- and anti-inflammatory cytokines secreted by activated TI cellular network may play a pivotal role in protection in the early stages of infection as observed during the COVID-19 pandemic in the younger age groups resulting in lower morbidity and mortality.

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“…Demethylated CNS1 in the Ifng locus was also found in human CIML NK cells after a resting period of 14 days ( 54 ). Additionally, it has been reported that the histone methyltransferase EZH2 plays a crucial role in CIML NK cells, since its pharmacological inhibition with UNC1999 limited the enhanced IFNγ production following IL-12/18-restimulation ( 61 ). These reports suggest that there are some epigenetic changes accompanying functional, transcriptional and metabolic reprogramming of IL-12/15/18-stimulated NK cells.…”

Section: Cytokine-induced Memory-like (Ciml) Nk Cellsmentioning

confidence: 99%

Cytokine-Induced Memory-Like NK Cells: From the Basics to Clinical Applications

et al. 2022

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Natural killer (NK) cells are lymphocytes with a key role in the defense against viral infections and tumor cells. Although NK cells are classified as innate lymphoid cells (ILCs), under certain circumstances they exhibit adaptive and memory-like features. The latter may be achieved, among others, by a brief stimulation with interleukin (IL)-12, IL-15 and IL-18. These cytokine-induced memory-like (CIML) NK cells resemble the trained immunity observed in myeloid cells. CIML NK cells undergo transcriptional, epigenetic and metabolic reprogramming that, along with changes in the expression of cell surface receptors and components of cytotoxic granules, are responsible for their enhanced effector functions after a resting period. In addition, these memory-like NK cells persist for a long time, which make them a good candidate for cancer immunotherapy. Currently, several clinical trials are testing CIML NK cells infusions to treat tumors, mostly hematological malignancies. In relapse/refractory acute myeloid leukemia (AML), the adoptive transfer of CIML NK cells is safe and complete clinical remissions have been observed. In our review, we sought to summarize the current knowledge about the generation and molecular basis of NK cell memory-like responses and the up-to-date results from clinical trials with CIML NK cells.

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EZH2 identifies the precursors of human natural killer cells with trained immunity

Cited by 8 publications

References 25 publications

BCG activation of trained immunity is associated with induction of cross reactive COVID-19 antibodies in a BCG vaccinated population

BCG activation of trained immunity is associated with induction of cross reactive COVID-19 antibodies in a BCG vaccinated population

BCG activation of trained immunity is associated with induction of cross reactive COVID-19 antibodies in a BCG vaccinated population

Cytokine-Induced Memory-Like NK Cells: From the Basics to Clinical Applications

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