scRNA-Seq Reveals Sustained Pro-Inflammation by Innate Immune Activation in In Utero HBV-Exposed Neonates of High HBsAg Mothers.
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| Titel: | scRNA-Seq Reveals Sustained Pro-Inflammation by Innate Immune Activation in In Utero HBV-Exposed Neonates of High HBsAg Mothers. |
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| Autoren: | Pahwa P; Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India., Singh R; Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India., Chattopadhyay P; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India., Mehta P; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India., Vyas AK; Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India.; Amrita Research Center, Delhi NCR, Amrita Vishwa Vidyapeetham, Faridabad, India., Patra S; Department of Obstetrics and Gynaecology, Lady Harding Medical College, New Delhi, India., Tyagi S; Department of Gynaecology and Obstetrics, Lok Nayak Jai Prakash Hospital, New Delhi, India., Pandey R; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India., Sarin SK; Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India., Trehanpati N; Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India. |
| Quelle: | Liver international : official journal of the International Association for the Study of the Liver [Liver Int] 2025 Dec; Vol. 45 (12), pp. e70405. |
| Publikationsart: | Journal Article |
| Sprache: | English |
| Info zur Zeitschrift: | Publisher: Wiley-Blackwell Country of Publication: United States NLM ID: 101160857 Publication Model: Print Cited Medium: Internet ISSN: 1478-3231 (Electronic) Linking ISSN: 14783223 NLM ISO Abbreviation: Liver Int Subsets: MEDLINE |
| Imprint Name(s): | Publication: Malden, MA : Wiley-Blackwell Original Publication: Oxford, UK : Blackwell Munksgaard, c2003- |
| MeSH-Schlagworte: | Immunity, Innate* , Hepatitis B Surface Antigens*/blood , Hepatitis B Surface Antigens*/immunology , Hepatitis B Vaccines*/immunology , Hepatitis B Vaccines*/administration & dosage , Infectious Disease Transmission, Vertical*/prevention & control , Hepatitis B*/immunology , Hepatitis B*/transmission , Hepatitis B*/prevention & control , Pregnancy Complications, Infectious*/immunology, Humans ; Female ; Infant, Newborn ; Pregnancy ; Hepatitis B virus/immunology ; RNA-Seq ; Adult ; Adaptive Immunity ; Male ; CD8-Positive T-Lymphocytes/immunology ; Single-Cell Analysis ; Inflammation/immunology ; Single-Cell Gene Expression Analysis |
| Abstract: | Background and Aim: High levels of HBV DNA and HBsAg titres increase the risk of mother-to-child transmission. Development of adaptive immunity post HBV vaccination in neonates born to HBsAg-positive mothers may be determined by maternal HBsAg titres. We analysed pre- and post-HBV vaccination immune status in neonates. Method: PBMCs were collected before and after vaccination for single cell multi-omics sequencing for infants born to mothers with low (Gr.1, sAg Lo 1.65 × 10 2 IU/mL) and high (Gr.2, sAg Hi 1.4 × 10 4 IU/mL) HBsAg titres. Integrative analysis of whole transcriptome and surface marker expression was done using the Seurat R package. Functional validation of single-cell data was performed through immunophenotyping in both groups. Results: scRNAseq revealed that, at pre-HBV vaccine, CD8 + T cells of neonates born to mothers with HBsAg Hi levels showed increased expression (p < 0.05) of TOX, CTLA4, PD1, LAG3, CD38 and CREM exhaustion markers and decreased expression of ATP1B3, MREG and TGFβ1 compared to sAg Lo . Monocytes and NK cells had elevated CXCR3, TNFSF9, HIVEP3, WDPCP, ATP6V1G2, IL-6, GMCSF and GCSF (p < 0.0001) driving the inflammation and mitochondrial biogenesis through MAP/ERK kinase in sAg Hi compared to sAg Lo . Post-vaccination, despite anti-HBs titre ≥ 10 IU/mL, sAg Hi , neonates showed persistently high TOX, CTLA4, PD1 and CREM in CD8 + T cells (p < 0.0001). Functional validations by immune phenotyping also showed higher expression of LAG3, PD1, TIGIT and BTLA (p < 0.05) on CD8 + T cells pre- and post-vaccination in sAg Hi compared to sAg Lo . Conclusion: HBV exposure compromises adaptive immunity at birth; despite post-vaccination anti-HBs titres generation, there was a sustained pro-inflammatory state by the innate immune activation via metabolic alterations that persisted in neonates born to sAg Hi mothers. (© 2025 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.) |
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| Grant Information: | VIR/78/2013/ECD-I Indian Council of Medical Research; BT/PR30213/MED/15/191/2018 Rajiv Gandhi Centre for Biotechnology, Department of Biotechnology, Ministry of Science and Technology, India |
| Contributed Indexing: | Keywords: adaptive immunity; hepatitis B virus; immune exhaustion; metabolic alteration; neonates; trained immunity; vaccination |
| Substance Nomenclature: | 0 (Hepatitis B Surface Antigens) 0 (Hepatitis B Vaccines) |
| Entry Date(s): | Date Created: 20251108 Date Completed: 20251108 Latest Revision: 20251108 |
| Update Code: | 20251108 |
| DOI: | 10.1111/liv.70405 |
| PMID: | 41204708 |
| Datenbank: | MEDLINE |
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Nájsť tento článok vo Web of Science | Abstract: | Background and Aim: High levels of HBV DNA and HBsAg titres increase the risk of mother-to-child transmission. Development of adaptive immunity post HBV vaccination in neonates born to HBsAg-positive mothers may be determined by maternal HBsAg titres. We analysed pre- and post-HBV vaccination immune status in neonates.<br />Method: PBMCs were collected before and after vaccination for single cell multi-omics sequencing for infants born to mothers with low (Gr.1, sAg <sup>Lo</sup> 1.65 × 10 <sup>2</sup> IU/mL) and high (Gr.2, sAg <sup>Hi</sup> 1.4 × 10 <sup>4</sup> IU/mL) HBsAg titres. Integrative analysis of whole transcriptome and surface marker expression was done using the Seurat R package. Functional validation of single-cell data was performed through immunophenotyping in both groups.<br />Results: scRNAseq revealed that, at pre-HBV vaccine, CD8 <sup>+</sup> T cells of neonates born to mothers with HBsAg <sup>Hi</sup> levels showed increased expression (p < 0.05) of TOX, CTLA4, PD1, LAG3, CD38 and CREM exhaustion markers and decreased expression of ATP1B3, MREG and TGFβ1 compared to sAg <sup>Lo</sup> . Monocytes and NK cells had elevated CXCR3, TNFSF9, HIVEP3, WDPCP, ATP6V1G2, IL-6, GMCSF and GCSF (p < 0.0001) driving the inflammation and mitochondrial biogenesis through MAP/ERK kinase in sAg <sup>Hi</sup> compared to sAg <sup>Lo</sup> . Post-vaccination, despite anti-HBs titre ≥ 10 IU/mL, sAg <sup>Hi</sup> , neonates showed persistently high TOX, CTLA4, PD1 and CREM in CD8 <sup>+</sup> T cells (p < 0.0001). Functional validations by immune phenotyping also showed higher expression of LAG3, PD1, TIGIT and BTLA (p < 0.05) on CD8 <sup>+</sup> T cells pre- and post-vaccination in sAg <sup>Hi</sup> compared to sAg <sup>Lo</sup> .<br />Conclusion: HBV exposure compromises adaptive immunity at birth; despite post-vaccination anti-HBs titres generation, there was a sustained pro-inflammatory state by the innate immune activation via metabolic alterations that persisted in neonates born to sAg <sup>Hi</sup> mothers.<br /> (© 2025 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.) |
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| ISSN: | 1478-3231 |
| DOI: | 10.1111/liv.70405 |