Maternal-fetal immune responses in pregnant women infected with SARS-CoV-2

被引:158
作者
Garcia-Flores, Valeria [1 ,2 ,3 ]
Romero, Roberto [1 ,2 ,4 ,5 ,6 ,7 ]
Xu, Yi [1 ,2 ,3 ]
Theis, Kevin [1 ,2 ,3 ,8 ]
Arenas-Hernandez, Marcia [1 ,2 ,3 ]
Miller, Derek [1 ,2 ,3 ]
Peyvandipour, Azam [1 ,2 ,3 ,6 ]
Galaz, Jose [1 ,2 ,3 ]
Levenson, Dustyn [1 ,2 ,3 ]
Bhatti, Gaurav [1 ,2 ,3 ]
Gershater, Meyer [1 ,2 ,3 ]
Pusod, Errile [1 ,2 ,3 ]
Kracht, David [1 ,2 ,3 ]
Florova, Violetta [1 ,2 ,3 ]
Leng, Yaozhu [1 ,2 ,3 ]
Tao, Li [1 ,2 ,3 ]
Faucett, Megan [1 ,2 ,3 ]
Para, Robert [1 ,2 ,3 ]
Hsu, Chaur-Dong [1 ,2 ,3 ,9 ]
Zhang, Gary [6 ]
Tarca, Adi [1 ,2 ,3 ,10 ]
Pique-Regi, Roger [1 ,2 ,3 ,6 ]
Gomez-Lopez, Nardhy [1 ,2 ,3 ,8 ]
机构
[1] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Div Obstet & Maternal Fetal Med, Div Intramural Res,NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA
[2] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Div Obstet & Maternal Fetal Med, Div Intramural Res,NIH,US Dept Hlth & Human Serv, Detroit, MI 48201 USA
[3] Wayne State Univ, Dept Obstet & Gynecol, Sch Med, Detroit, MI 48201 USA
[4] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA
[5] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA
[6] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA
[7] Detroit Med Ctr, Detroit, MI 48201 USA
[8] Wayne State Univ, Dept Biochem Microbiol & Immunol, Sch Med, Detroit, MI 48201 USA
[9] Wayne State Univ, Dept Physiol, Sch Med, Detroit, MI 48201 USA
[10] Wayne State Univ, Dept Comp Sci, Coll Engn, Detroit, MI 48201 USA
基金
美国国家卫生研究院;
关键词
T-CELLS; ASSOCIATION; INFERENCE; PLACENTA; OUTCOMES; IMPACT;
D O I
10.1038/s41467-021-27745-z
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Pregnant women represent a high-risk population for severe/critical COVID-19 and mortality. However, the maternal-fetal immune responses initiated by SARS-CoV-2 infection, and whether this virus is detectable in the placenta, are still under investigation. Here we show that SARS-CoV-2 infection during pregnancy primarily induces unique inflammatory responses at the maternal-fetal interface, which are largely governed by maternal T cells and fetal stromal cells. SARS-CoV-2 infection during pregnancy is also associated with humoral and cellular immune responses in the maternal blood, as well as with a mild cytokine response in the neonatal circulation (i.e., umbilical cord blood), without compromising the T-cell repertoire or initiating IgM responses. Importantly, SARS-CoV-2 is not detected in the placental tissues, nor is the sterility of the placenta compromised by maternal viral infection. This study provides insight into the maternal-fetal immune responses triggered by SARS-CoV-2 and emphasizes the rarity of placental infection. As pregnant women are considered vulnerable to SARSCoV-2 infection, it is important to investigate the actual risks involved. The authors show here that, while a T cell-dominant inflammatory response is observed at the maternal-foetal interface, the virus remains undetectable in the placenta but triggers specific immune responses in the neonatal (umbilical cord blood) circulation.
引用
收藏
页数:20
相关论文
共 113 条
[1]   Ribosome-Targeting Antibiotics Impair T Cell Effector Function and Ameliorate Autoimmunity by Blocking Mitochondrial Protein Synthesis [J].
Almeida, Luis ;
Dhillon-LaBrooy, Ayesha ;
Castro, Carla N. ;
Adossa, Nigatu ;
Carriche, Guilhermina M. ;
Guderian, Melanie ;
Lippens, Saskia ;
Dennerlein, Sven ;
Hesse, Christina ;
Lambrecht, Bart N. ;
Berod, Luciana ;
Schauser, Leif ;
Blazar, Bruce R. ;
Kalesse, Markus ;
Mueller, Rolf ;
Moita, Luis F. ;
Sparwasser, Tim .
IMMUNITY, 2021, 54 (01) :68-+
[2]   Enhancing droplet-based single-nucleus RNA-seq resolution using the semi-supervised machine learning classifier DIEM [J].
Alvarez, Marcus ;
Rahmani, Elior ;
Jew, Brandon ;
Garske, Kristina M. ;
Miao, Zong ;
Benhammou, Jihane N. ;
Ye, Chun Jimmie ;
Pisegna, Joseph R. ;
Pietilainen, Kirsi H. ;
Halperin, Eran ;
Pajukanta, Paivi .
SCIENTIFIC REPORTS, 2020, 10 (01)
[3]  
Anderson MJ., Wiley StatsRef: Statistics Reference Online2017, P1
[4]   Symptoms and Critical Illness Among Obstetric Patients With Coronavirus Disease 2019 (COVID-19) Infection [J].
Andrikopoulou, Maria ;
Madden, Nigel ;
Wen, Timothy ;
Aubey, Janice J. ;
Aziz, Aleha ;
Baptiste, Caitlin D. ;
Breslin, Noelle ;
D'Alton, Mary E. ;
Fuchs, Karin M. ;
Goffman, Dena ;
Gyamfi-Bannerman, Cynthia ;
Matseoane-Peterssen, Dara N. ;
Miller, Russell S. ;
Sheen, Jean-Ju ;
Simpson, Lynn L. ;
Sutton, Desmond ;
Zork, Noelia ;
Friedman, Alexander M. .
OBSTETRICS AND GYNECOLOGY, 2020, 136 (02) :291-299
[5]  
[Anonymous], 2019, Vegan: Community Ecology Package
[6]  
[Anonymous], 2019, R: a language and environment for statistical computing
[7]   Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage [J].
Aran, Dvir ;
Looney, Agnieszka P. ;
Liu, Leqian ;
Wu, Esther ;
Fong, Valerie ;
Hsu, Austin ;
Chak, Suzanna ;
Naikawadi, Ram P. ;
Wolters, Paul J. ;
Abate, Adam R. ;
Butte, Atul J. ;
Bhattacharya, Mallar .
NATURE IMMUNOLOGY, 2019, 20 (02) :163-+
[8]   Compromised SARS-CoV-2-specific placental antibody transfer [J].
Atyeo, Caroline ;
Pullen, Krista M. ;
Bordt, Evan A. ;
Fischinger, Stephanie ;
Burke, John ;
Michell, Ashlin ;
Slein, Matthew D. ;
Loos, Carolin ;
Shook, Lydia L. ;
Boatin, Adeline A. ;
Yockey, Laura J. ;
Pepin, David ;
Meinsohn, Marie-Charlotte ;
Nguyen, Ngoc Minh Phuong ;
Chauvin, Maeva ;
Roberts, Drucilla ;
Goldfarb, Ilona T. ;
Matute, Juan D. ;
James, Kaitlyn E. ;
Yonker, Lael M. ;
Bebell, Lisa M. ;
Kaimal, Anjali J. ;
Gray, Kathryn J. ;
Lauffenburger, Douglas ;
Edlow, Andrea G. ;
Alter, Galit .
CELL, 2021, 184 (03) :628-+
[9]   Neonatal encephalopathy: Association of cytokines with MR spectroscopy and outcome [J].
Bartha, AI ;
Foster-Barber, A ;
Miller, SP ;
Vigneron, DB ;
Glidden, DV ;
Barkovich, AJ ;
Ferriero, DM .
PEDIATRIC RESEARCH, 2004, 56 (06) :960-966
[10]   Dimensionality reduction for visualizing single-cell data using UMAP [J].
Becht, Etienne ;
McInnes, Leland ;
Healy, John ;
Dutertre, Charles-Antoine ;
Kwok, Immanuel W. H. ;
Ng, Lai Guan ;
Ginhoux, Florent ;
Newell, Evan W. .
NATURE BIOTECHNOLOGY, 2019, 37 (01) :38-+