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AuthorAgostinis, Chiara
AuthorToffoli, Miriam
AuthorSpazzapan, Mariagiulia
AuthorBalduit, Andrea
AuthorZito, Gabriella
AuthorMangogna, Alessandro
AuthorZupin, Luisa
AuthorSalviato, Tiziana
AuthorMaiocchi, Serena
AuthorRomano, Federico
AuthorCrovella, Sergio
AuthorFontana, Francesco
AuthorBraga, Luca
AuthorConfalonieri, Marco
AuthorRicci, Giuseppe
AuthorKishore, Uday
AuthorBulla, Roberta
Available date2022-10-24T09:00:46Z
Publication Date2022-09-13
Publication NameFrontiers in Immunology
Identifierhttp://dx.doi.org/10.3389/fimmu.2022.957224
CitationAgostinis C, Toffoli M, Spazzapan M, Balduit A, Zito G, Mangogna A, Zupin L, Salviato T, Maiocchi S, Romano F, Crovella S, Fontana F, Braga L, Confalonieri M, Ricci G, Kishore U and Bulla R (2022) SARS-CoV-2 modulates virus receptor expression in placenta and can induce trophoblast fusion, inflammation and endothelial permeability. Frontiers in immunology. 13:957224. doi: 10.3389/fimmu.2022.957224
URIhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85138867288&origin=inward
URIhttp://hdl.handle.net/10576/35352
AbstractSARS-CoV-2 is a devastating virus that induces a range of immunopathological mechanisms including cytokine storm, apoptosis, inflammation and complement and coagulation pathway hyperactivation. However, how the infection impacts pregnant mothers is still being worked out due to evidence of vertical transmission of the SARS-CoV-2, and higher incidence of pre-eclampsia, preterm birth, caesarian section, and fetal mortality. In this study, we assessed the levels of the three main receptors of SARS-CoV-2 (ACE2, TMPRSS2 and CD147) in placentae derived from SARS-CoV-2 positive and negative mothers. Moreover, we measured the effects of Spike protein on placental cell lines, in addition to their susceptibility to infection. SARS-CoV-2 negative placentae showed elevated levels of CD147 and considerably low amount of TMPRSS2, making them non-permissive to infection. SARS-CoV-2 presence upregulated TMPRSS2 expression in syncytiotrophoblast and cytotrophoblast cells, thereby rendering them amenable to infection. The non-permissiveness of placental cells can be due to their less fusogenicity due to infection. We also found that Spike protein was capable of inducing pro-inflammatory cytokine production, syncytiotrophoblast apoptosis and increased vascular permeability. These events can elicit pre-eclampsia-like syndrome that marks a high percentage of pregnancies when mothers are infected with SARS-CoV-2. Our study raises important points relevant to SARS-CoV-2 mediated adverse pregnancy outcomes.
SponsorFerring COVID-19 Investigational Grant (GRAVISAR to RB)
Languageen
PublisherFrontiers Media
SubjectACE2
CD147
pregnancy
SARS-CoV-2
TMPRSS2
TitleSARS-CoV-2 modulates virus receptor expression in placenta and can induce trophoblast fusion, inflammation and endothelial permeability
TypeArticle
Pagination1-20
Volume Number13
ESSN1664-3224
dc.accessType Open Access


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