Immune Profiling of Cord Blood From Preterm and Term Infants Reveals Distinct Differences in Pro-Inflammatory Responses

Anderson, Jeremy; Thang, Cao Minh; Thanh, Lê Quang; Dai, Vo Thi Trang; Phan, Van Thanh; Nhu, Bùi Thị Hồng; Trang, Do Ngoc Xuan; Trinh, Phan Thi Phuong; Nguyen, Thuong Vu; Toàn, Nguyễn Trọng; Harpur, Christopher M.; Mulholland, Kim; Pellicci, Daniel G.; Ha, Lien Anh; Licciardi, Paul V.

doi:10.3389/fimmu.2021.777927

Cited by 30 publications

(26 citation statements)

References 41 publications

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“…Our analyses of immune cell profiles showed that decreased odds of being a preterm infant were associated with increased CD4T cells when NDMI 450 was accounted for, and with increased NK and B cell proportions when NDMI 450 was not accounted for. This conflicts with published literature reports that preterm infants exhibited reduced frequencies of CD56 bright NK cells and increased frequencies of CD4+ T cells and transitional B cells [ 19 ]. Additionally, our analyses of glucose tolerance showed an increase in CD8T proportions was associated with a significant decrease in odds of GDM.…”

Section: Discussioncontrasting

confidence: 95%

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Evaluation of cross-platform compatibility of a DNA methylation-based glucocorticoid response biomarker

et al. 2022

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Background Identifying blood-based DNA methylation patterns is a minimally invasive way to detect biomarkers in predicting age, characteristics of certain diseases and conditions, as well as responses to immunotherapies. As microarray platforms continue to evolve and increase the scope of CpGs measured, new discoveries based on the most recent platform version and how they compare to available data from the previous versions of the platform are unknown. The neutrophil dexamethasone methylation index (NDMI 850) is a blood-based DNA methylation biomarker built on the Illumina MethylationEPIC (850K) array that measures epigenetic responses to dexamethasone (DEX), a synthetic glucocorticoid often administered for inflammation. Here, we compare the NDMI 850 to one we built using data from the Illumina Methylation 450K (NDMI 450). Results The NDMI 450 consisted of 22 loci, 15 of which were present on the NDMI 850. In adult whole blood samples, the linear composite scores from NDMI 450 and NDMI 850 were highly correlated and had equivalent predictive accuracy for detecting DEX exposure among adult glioma patients and non-glioma adult controls. However, the NDMI 450 scores of newborn cord blood were significantly lower than NDMI 850 in samples measured with both assays. Conclusions We developed an algorithm that reproduces the DNA methylation glucocorticoid response score using 450K data, increasing the accessibility for researchers to assess this biomarker in archived or publicly available datasets that use the 450K version of the Illumina BeadChip array. However, the NDMI850 and NDMI450 do not give similar results in cord blood, and due to data availability limitations, results from sample types of newborn cord blood should be interpreted with care.

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Section: Discussioncontrasting

confidence: 95%

“…Immune cells in term and preterm labor participate in various phases of the pregnancy. Compared to term infants, preterm infants were observed to have lower proportions of CD56 bright NK cells, CD8+ T cells, and γδ T cells, and increased levels of CD4+ T cells and transitional B cells [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of cross-platform compatibility of a DNA methylation-based glucocorticoid response biomarker

et al. 2022

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“…Previous studies reported dampened responses by human UCB monocytes of babies born to mothers with obesity (15,28,39,40) as well as by splenocytes from pups born to obese dams to LPS stimulation (41). Additional studies indicated increased airway reactivity and aberrant responses to RSV in pups born to dams fed a HFD during gestation (22).…”

Section: Discussionmentioning

confidence: 98%

Impact of pregravid obesity on anti-microbial fetal monocyte response

Sureshchandra

Doratt

Mendoza

et al. 2022

Preprint

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Maternal pre-pregnancy (pregravid) obesity is associated with adverse outcomes for both mother and offspring. Amongst the complications for the offspring is increased susceptibility and severity of neonatal infections necessitating admission to the intensive care unit, notably bacterial sepsis and enterocolitis. Previous studies have reported aberrant responses to LPS and polyclonal stimulation by umbilical cord blood monocytes that were mediated by alterations in the epigenome. In this study, we show that pregravid obesity dysregulates umbilical cord blood monocyte responses to bacterial and viral pathogens. Specifically, interferon-stimulated gene expression and inflammatory responses to E. coli and respiratory syncytial virus (RSV) were significantly dampened. Although upstream signaling events were comparable, translocation of the key transcription factor NFkB and chromatin accessibility at pro-inflammatory gene promoters following TLR stimulation was significantly attenuated. Using a rhesus macaque model of western style diet induced obesity, we further demonstrate that this defect is detected in fetal peripheral monocytes and tissue-resident macrophages during gestation. Collectively, these data indicate that maternal obesity and high-fat diet present metabolic, signaling, and epigenetic impediments to pathogen recognition in fetal innate immune cells that result in a state of immune paralysis during gestation and at birth.

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“…Further studies have revealed differences between the blood of preterm and term infants: Anderson et al reported reduced frequencies of monocytes and CD56 bright NK cells, as well as CD8+ T-cells, and γδ T-cells in preterm infants [ 35 ]. Moreover, controversial data exist regarding the amount of proinflammatory interleukin-6 (IL-6) in cord blood: While Anderson et al reported elevated levels in preterm infants, Sullivan et al detected lower levels in comparison to term infants [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Preterm ETs Are Significantly Reduced Compared with Adults and Partially Reduced Compared with Term Infants

et al. 2022

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The release of DNA by cells during extracellular trap (ET) formation is a defense function of neutrophils and monocytes. Neutrophil ET (NET) formation in term infants is reduced compared to adults. Objective: The aim was to quantify NET and monocyte ET (MET) release and the respective key enzymes myeloperoxidase (MPO) and neutrophil elastase (NE) in preterm infants. In this prospective explorative study, ET induction was stimulated by N-formylmethionine-leucyl-phenylalanine (fMLP), phorbol 12-myristate 13-acetate (PMA), lipopolysaccharide (LPS), and lipoteichoic acid (LTA) in the cord blood of preterm infants (n = 55, 23–36 weeks) compared to term infants and adults. METs were quantified by microscopy, and NETs by microscopy and flow cytometry. We also determined the MPO levels within NETs and the intracellular concentrations of NE and MPO in neutrophils. The percentage of neutrophils releasing ET was significantly reduced for preterm infants compared to adults for all stimulants, and with a 68% further reduction for PMA compared to term infants (p = 0.0141). The NET area was not reduced except for when fMLP was administered. The amount of MPO in NET-producing cells was reduced in preterm infants compared to term infants. For preterm infants, but not term infants, the percentage of monocytes releasing ETs was significantly reduced compared to healthy adults for LTA and LPS stimulation. Conclusion: In preterm infants, ETs are measurable parts of the innate immune system, but are released in a reduced percentage of cells compared to adults.

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Immune Profiling of Cord Blood From Preterm and Term Infants Reveals Distinct Differences in Pro-Inflammatory Responses

Cited by 30 publications

References 41 publications

Evaluation of cross-platform compatibility of a DNA methylation-based glucocorticoid response biomarker

Evaluation of cross-platform compatibility of a DNA methylation-based glucocorticoid response biomarker

Impact of pregravid obesity on anti-microbial fetal monocyte response

Preterm ETs Are Significantly Reduced Compared with Adults and Partially Reduced Compared with Term Infants

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