Decidual production of interferon lambda in response to ZIKV persistence: Clinical evidence and in vitro modelling.

Autor:	Azamor T; Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Cunha DP; Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Nobre Pires KS; Federal University of Alagoas, Maceió, Brazil., Lira Tanabe EL; Federal University of Alagoas, Maceió, Brazil., Melgaço JG; Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Vieira da Silva AM; Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Ribeiro-Alves M; Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Calvo TL; Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Tubarão LN; Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., da Silva J; Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Fernandes CB; Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Fonseca de Souza A; Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Torrentes de Carvalho A; Federal Fluminense University, Niterói, Brazil., Avvad-Portari E; Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., da Cunha Guida L; Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Gomes L; Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Lopes Moreira ME; Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Dinis Ano Bom AP; Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Cristina da Costa Neves P; Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Missailidis S; Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Vasconcelos Z; Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Borbely AU; Federal University of Alagoas, Maceió, Brazil., Moraes MO; Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
Jazyk:	angličtina
Zdroj:	Heliyon [Heliyon] 2024 May 03; Vol. 10 (9), pp. e30613. Date of Electronic Publication: 2024 May 03 (Print Publication: 2024).
DOI:	10.1016/j.heliyon.2024.e30613
Abstrakt:	Zika virus (ZIKV) infections during pregnancy can result in Congenital Zika Syndrome (CZS), a range of severe neurological outcomes in fetuses that primarily occur during early gestational stages possibly due to placental damage. Although some placentas can maintain ZIKV persistence for weeks or months after the initial infection and diagnosis, the impact of this viral persistence is still unknown. Here, we aimed to investigate the immunological repercussion of ZIKV persistence in term placentas. As such, term placentas from 64 pregnant women diagnosed with Zika in different gestational periods were analyzed by ZIKV RT-qPCR, examination of decidua and placental villous histopathology, and expression of inflammation-related genes and IFNL1-4 . Subsequently, we explored primary cultures of term decidual Extravillous Trophoblasts (EVTs) and Term Chorionic Villi (TCV) explants, as in vitro models to access the immunological consequences of placental ZIKV infection. Placenta from CZS cases presented low IFNL1-4 expression, evidencing the critical protective role of theses cytokines in the clinical outcome. Term placentas cleared for ZIKV showed increased levels of IFNL1 , 3 , and 4 , whether viral persistence was related with a proinflammatory profile. Conversely, upon ZIKV persistence placentas with decidual inflammation showed high IFNL1-4 levels. In vitro experiments showed that term EVTs are more permissive, and secreted higher levels of IFN-α2 and IFN-λ1 compared to TCV explants. The results suggest that, upon ZIKV persistence, the maternal-skewed decidua contributes to placental inflammatory and antiviral signature, through chronic deciduitis and IFNL upregulation. Although further studies are needed to elucidate the mechanisms underlying the decidual responses against ZIKV. Hence, this study presents unique insights and valuable in vitro models for evaluating the immunological landscape of placentas upon ZIKV persistence. Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2024 The Authors.)
Databáze:	MEDLINE
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