Single-cell RNA-sequencing highlights a curtailed NK cell function in convalescent COVID-19 pregnant women

作者：Madhuri S. Salker, Nor Haslinda Abd Aziz, Natalia Prodan, Zhiqi Yang, Aditya Kumar Lankapalli, Katrin Lazar, Mohamad Nasir Shafiee, Ersoy Kocak, Harivignesh Ganesan, Surya Sekhar Pal, Omer Khalid, Norhana Mohd Kasim, Aida Kalok, Norashikin Abdul Fuad, Alfred Lennart Bissinger, Tina Ganzenmueller, Thomas Iftner, Karl Oliver Kagan, Stephan Ossowski, Nicolas Casadei, Sara Y. Brucker, Olaf Rieß, Yogesh Singh, Deutsche COVID-19 OMICS Initiative (DeCOI) · 发表于：Frontiers in Immunology · 年份：2025 · DOI：10.3389/fimmu.2025.1560391 · 被引用次数：2 · 研究领域：COVID-19 Impact on Reproduction、Reproductive System and Pregnancy、Gestational Diabetes Research and Management

Introduction During gestation the immune system undergoes dramatic remodelling to protect the maternal-fetal dyad from infections whilst also preventing fetal rejection. We investigated how SARS-CoV-2 modifies the immune landscape during infection and in recovered pregnant women. Methods We immunophenotyped our two independent geographical cohorts using a 14-colour flow cytometry panel (surface and intracellular staining). We estimated cytokines and SARS-CoV-2 IgG antibodies in validation cohort using a multiplexd flow cytometry panel. Single-cell RNA sequencing (scRNA-seq) was performed using a Chromium Single Cell 3’ Gel Bead Chip and Library Kit from 10x Genomics (Drop-seq method). Furthermore, we estimated the cytotoxic functions of natural killer (NK) cells by flow cytometry using surface and intracellular staining. Results Using two independent geographical cohorts, we identified that NK cells had a sustained reduction during active infection and after recovery. Further, scRNA-seq data revealed that infection with SARS-CoV-2 rewired the gene expression profile of NK, monocytes, CD4 + , CD8 + effector T cells and antibody producing B cells in convalescent pregnant women. Several gene pathways associated with cytotoxic function, interferon signalling type I & II, and pro- and anti-inflammatory functions in NK and CD8 + cytotoxic T cells were attenuated in recovered pregnant patients compared with healthy pregnancies. We validated our scRNA-seq of NK cells from con...