Maternal SARS-CoV-2 infection elicits sexually dimorphic placental immune responses

被引：71

作者：

Bordt, Evan A. ^{[1
]}

Shook, Lydia L. ^{[2
,3
]}

Atyeo, Caroline ^{[4
,5
]}

Pullen, Krista M. ^{[6
]}

De Guzman, Rose M. ^{[2
,3
]}

Meinsohn, Marie-Charlotte ^{[7
]}

Chauvin, Maeva ^{[7
]}

Fischinger, Stephanie ^{[4
]}

Yockey, Laura J. ^{[2
,8
]}

James, Kaitlyn ^{[2
]}

Lima, Rosiane ^{[9
]}

Yonker, Lael M. ^{[9
]}

Fasano, Alessio ^{[9
,10
]}

Brigida, Sara ^{[2
,3
]}

Bebell, Lisa M. ^{[8
]}

Roberts, Drucilla J. ^{[11
]}

Pepin, David ^{[7
]}

Huh, Jun R. ^{[12
,13
,14
]}

Bilbo, Staci D. ^{[1
,15
]}

Li, Jonathan Z. ^{[16
]}

Kaimal, Anjali ^{[2
]}

Schust, Danny J. ^{[17
]}

Gray, Kathryn J. ^{[18
]}

Lauffenburger, Douglas ^{[6
]}

Alter, Galit ^{[4
]}

Edlow, Andrea G. ^{[2
,3
]}

机构：

[1] Massachusetts Gen Hosp, Lurie Ctr Autism, Harvard Med Sch, Dept Pediat, Boston, MA 02129 USA

[2] Massachusetts Gen Hosp, Harvard Med Sch, Dept Obstet & Gynecol, Boston, MA 02114 USA

[3] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA

[4] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA

[5] Harvard Univ, Div Med Sci, PhD Program Virol, Boston, MA 02115 USA

[6] MIT, Dept Biol Engn, Cambridge, MA 02142 USA

[7] Massachusetts Gen Hosp, Harvard Med Sch, Dept Surg, Pediat Surg Res Labs, Boston, MA 02114 USA

[8] Massachusetts Gen Hosp, Harvard Med Sch, Dept Med, Boston, MA 02114 USA

[9] Massachusetts Gen Hosp, Mucosal Immunol & Biol Res Ctr, Dept Pediat, Boston, MA 02129 USA

[10] European Biomed Res Inst Salerno EBRIS, Salerno, Italy

[11] Massachusetts Gen Hosp, Harvard Med Sch, Dept Pathol, Boston, MA 02114 USA

[12] Harvard Med Sch, Blavatnik Inst, Dept Immunol, Boston, MA 02115 USA

[13] Harvard Med Sch, Evergrande Ctr Immunol Dis, Boston, MA 02115 USA

[14] Brigham & Womens Hosp, Boston, MA 02115 USA

[15] Duke Univ, Dept Psychol & Neurosci, Durham, NC 27708 USA

[16] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA

[17] Univ Missouri, Dept Obstet Gynecol & Womens Hlth, Columbia, MO 65201 USA

[18] Brigham & Womens Hosp, Harvard Med Sch, Dept Obstet & Gynecol, Boston, MA 02115 USA

来源：

SCIENCE TRANSLATIONAL MEDICINE | 2021年 / 13卷 / 617期

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

SEX-DIFFERENCES; ANTIBODY TRANSFER; INTERFERON-GAMMA; HIV-INFECTION; I-INTERFERON; FC-RECEPTOR; FETAL SEX; EXPRESSION; INFLAMMATION; TRANSMISSION;

D O I：

10.1126/scitranslmed.abi7428

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

There is a persistent bias toward higher prevalence and increased severity of coronavirus disease 2019 (COVID-19) in males. Underlying mechanisms accounting for this sex difference remain incompletely understood. Interferon responses have been implicated as a modulator of COVID-19 disease in adults and play a key role in the placental antiviral response. Moreover, the interferon response has been shown to alter Fc receptor expression and therefore may affect placental antibody transfer. Here, we examined the intersection of maternal-fetal antibody transfer, viral-induced placental interferon responses, and fetal sex in pregnant women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Placental Fc receptor abundance, interferon-stimulated gene (ISG) expression, and SARS-CoV-2 antibody transfer were interrogated in 68 human pregnancies. Sexually dimorphic expression of placental Fc receptors, ISGs and proteins, and interleukin-10 was observed after maternal SARS-CoV-2 infection, with up-regulation of these features in placental tissue of pregnant individuals with male fetuses. Reduced maternal SARS-CoV-2-specific antibody titers and impaired placental antibody transfer were also observed in pregnancies with a male fetus. These results demonstrate fetal sex-specific maternal and placental adaptive and innate immune responses to SARS-CoV-2.

引用

页数：15

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