Robust innate immune responses at the placenta during early gestation may limit in utero HIV transmission.

In 2019, >90% of new HIV infections in infants globally occurred vertically. Studies suggest intrauterine transmission most often occurs in the third trimester; however, there are no mechanistic studies to support these observations. We therefore obtained early/mid-gestation and term placentae fr...

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Autores principales:	Erica L Johnson, Dominika Swieboda, Amanda Olivier, Elizabeth Ann L Enninga, Rana Chakraborty
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/7a26c4f025c342bea5c42770fcd40fb7
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spelling	oai:doaj.org-article:7a26c4f025c342bea5c42770fcd40fb72021-12-02T20:00:15ZRobust innate immune responses at the placenta during early gestation may limit in utero HIV transmission.1553-73661553-737410.1371/journal.ppat.1009860https://doaj.org/article/7a26c4f025c342bea5c42770fcd40fb72021-08-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1009860https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374In 2019, >90% of new HIV infections in infants globally occurred vertically. Studies suggest intrauterine transmission most often occurs in the third trimester; however, there are no mechanistic studies to support these observations. We therefore obtained early/mid-gestation and term placentae from 20 HIV/Hepatitis B/CMV negative women. Isolated primary placental macrophages (Hofbauer cells [HCs]) were exposed to HIV-1BaL and/or interferon (IFN)-α, IFN-β, IFN-λ1, and RIG-I-like receptor (RLR) agonists. qRT-PCR, FACS, ELISA, Luminex, and Western blot analyses determined expression of activation markers, co-receptors, viral antigen, cytokines, antiviral genes, and host proteins. Early gestation HCs express higher levels of CCR5 and exhibit a more activated phenotype. Despite downregulation of CCR5, term HCs were more susceptible to HIV replication. Early gestation HCs displayed a more activated phenotype than term HCs and HIV exposure lead to the further up-regulation of T-cell co-stimulatory and MHC molecules. Limited HIV replication in early/mid gestation HCs was associated with increased secretion of anti-inflammatory cytokines, chemokines, and a more robust antiviral immune response. In contrast, term HCs were more susceptible to HIV replication, associated with dampening of IFN-induced STAT1 and STAT2 protein activation. Treatment of early/mid gestation and term HCs, with type I IFNs or RLR agonists reduced HIV replication, underscoring the importance of IFN and RLR signaling in inducing an antiviral state. Viral recognition and antiviral immunity in early gestation HCs may prevent in utero HIV infection, whereas diminished antiviral responses at term can facilitate transmission. Defining mechanisms and specific timing of vertical transmission are critical for the development of specific vaccines and antiviral therapeutics to prevent new HIV infections in children globally.Erica L JohnsonDominika SwiebodaAmanda OlivierElizabeth Ann L EnningaRana ChakrabortyPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 8, p e1009860 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Erica L Johnson Dominika Swieboda Amanda Olivier Elizabeth Ann L Enninga Rana Chakraborty Robust innate immune responses at the placenta during early gestation may limit in utero HIV transmission.
description	In 2019, >90% of new HIV infections in infants globally occurred vertically. Studies suggest intrauterine transmission most often occurs in the third trimester; however, there are no mechanistic studies to support these observations. We therefore obtained early/mid-gestation and term placentae from 20 HIV/Hepatitis B/CMV negative women. Isolated primary placental macrophages (Hofbauer cells [HCs]) were exposed to HIV-1BaL and/or interferon (IFN)-α, IFN-β, IFN-λ1, and RIG-I-like receptor (RLR) agonists. qRT-PCR, FACS, ELISA, Luminex, and Western blot analyses determined expression of activation markers, co-receptors, viral antigen, cytokines, antiviral genes, and host proteins. Early gestation HCs express higher levels of CCR5 and exhibit a more activated phenotype. Despite downregulation of CCR5, term HCs were more susceptible to HIV replication. Early gestation HCs displayed a more activated phenotype than term HCs and HIV exposure lead to the further up-regulation of T-cell co-stimulatory and MHC molecules. Limited HIV replication in early/mid gestation HCs was associated with increased secretion of anti-inflammatory cytokines, chemokines, and a more robust antiviral immune response. In contrast, term HCs were more susceptible to HIV replication, associated with dampening of IFN-induced STAT1 and STAT2 protein activation. Treatment of early/mid gestation and term HCs, with type I IFNs or RLR agonists reduced HIV replication, underscoring the importance of IFN and RLR signaling in inducing an antiviral state. Viral recognition and antiviral immunity in early gestation HCs may prevent in utero HIV infection, whereas diminished antiviral responses at term can facilitate transmission. Defining mechanisms and specific timing of vertical transmission are critical for the development of specific vaccines and antiviral therapeutics to prevent new HIV infections in children globally.
format	article
author	Erica L Johnson Dominika Swieboda Amanda Olivier Elizabeth Ann L Enninga Rana Chakraborty
author_facet	Erica L Johnson Dominika Swieboda Amanda Olivier Elizabeth Ann L Enninga Rana Chakraborty
author_sort	Erica L Johnson
title	Robust innate immune responses at the placenta during early gestation may limit in utero HIV transmission.
title_short	Robust innate immune responses at the placenta during early gestation may limit in utero HIV transmission.
title_full	Robust innate immune responses at the placenta during early gestation may limit in utero HIV transmission.
title_fullStr	Robust innate immune responses at the placenta during early gestation may limit in utero HIV transmission.
title_full_unstemmed	Robust innate immune responses at the placenta during early gestation may limit in utero HIV transmission.
title_sort	robust innate immune responses at the placenta during early gestation may limit in utero hiv transmission.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/7a26c4f025c342bea5c42770fcd40fb7
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Robust innate immune responses at the placenta during early gestation may limit in utero HIV transmission.

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