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Interferon Lambda Signals in Maternal Tissues to Exert Protective and Pathogenic Effects in a Gestational Stage-Dependent Manner

Interferon lambda (IFN-λ) (type III IFN) is constitutively secreted from human placental cells in culture and reduces Zika virus (ZIKV) transplacental transmission in mice. However, the roles of IFN-λ during healthy pregnancy and in restricting congenital infection remain unclear. Here, we used mice...

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Autores principales: Casazza, Rebecca L., Philip, Drake T., Lazear, Helen M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9239100/
https://www.ncbi.nlm.nih.gov/pubmed/35471083
http://dx.doi.org/10.1128/mbio.03857-21
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author Casazza, Rebecca L.
Philip, Drake T.
Lazear, Helen M.
author_facet Casazza, Rebecca L.
Philip, Drake T.
Lazear, Helen M.
author_sort Casazza, Rebecca L.
collection PubMed
description Interferon lambda (IFN-λ) (type III IFN) is constitutively secreted from human placental cells in culture and reduces Zika virus (ZIKV) transplacental transmission in mice. However, the roles of IFN-λ during healthy pregnancy and in restricting congenital infection remain unclear. Here, we used mice lacking the IFN-λ receptor (Ifnlr1(−/−)) to generate pregnancies lacking either maternal or fetal IFN-λ responsiveness and found that the antiviral effect of IFN-λ resulted from signaling exclusively in maternal tissues. This protective effect depended on gestational stage, as infection earlier in pregnancy (E7 rather than E9) resulted in enhanced transplacental transmission of ZIKV. In Ifnar1(−/−) dams, which sustain robust ZIKV infection, maternal IFN-λ signaling caused fetal resorption and intrauterine growth restriction. Pregnancy pathology elicited by poly(I·C) treatment also was mediated by maternal IFN-λ signaling, specifically in maternal leukocytes, and also occurred in a gestational stage-dependent manner. These findings identify an unexpected effect of IFN-λ signaling, specifically in maternal (rather than placental or fetal) tissues, which is distinct from the pathogenic effects of IFN-αβ (type I IFN) during pregnancy. These results highlight the complexity of immune signaling at the maternal-fetal interface, where disparate outcomes can result from signaling at different gestational stages.
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spelling pubmed-92391002022-06-29 Interferon Lambda Signals in Maternal Tissues to Exert Protective and Pathogenic Effects in a Gestational Stage-Dependent Manner Casazza, Rebecca L. Philip, Drake T. Lazear, Helen M. mBio Research Article Interferon lambda (IFN-λ) (type III IFN) is constitutively secreted from human placental cells in culture and reduces Zika virus (ZIKV) transplacental transmission in mice. However, the roles of IFN-λ during healthy pregnancy and in restricting congenital infection remain unclear. Here, we used mice lacking the IFN-λ receptor (Ifnlr1(−/−)) to generate pregnancies lacking either maternal or fetal IFN-λ responsiveness and found that the antiviral effect of IFN-λ resulted from signaling exclusively in maternal tissues. This protective effect depended on gestational stage, as infection earlier in pregnancy (E7 rather than E9) resulted in enhanced transplacental transmission of ZIKV. In Ifnar1(−/−) dams, which sustain robust ZIKV infection, maternal IFN-λ signaling caused fetal resorption and intrauterine growth restriction. Pregnancy pathology elicited by poly(I·C) treatment also was mediated by maternal IFN-λ signaling, specifically in maternal leukocytes, and also occurred in a gestational stage-dependent manner. These findings identify an unexpected effect of IFN-λ signaling, specifically in maternal (rather than placental or fetal) tissues, which is distinct from the pathogenic effects of IFN-αβ (type I IFN) during pregnancy. These results highlight the complexity of immune signaling at the maternal-fetal interface, where disparate outcomes can result from signaling at different gestational stages. American Society for Microbiology 2022-04-26 /pmc/articles/PMC9239100/ /pubmed/35471083 http://dx.doi.org/10.1128/mbio.03857-21 Text en Copyright © 2022 Casazza et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Casazza, Rebecca L.
Philip, Drake T.
Lazear, Helen M.
Interferon Lambda Signals in Maternal Tissues to Exert Protective and Pathogenic Effects in a Gestational Stage-Dependent Manner
title Interferon Lambda Signals in Maternal Tissues to Exert Protective and Pathogenic Effects in a Gestational Stage-Dependent Manner
title_full Interferon Lambda Signals in Maternal Tissues to Exert Protective and Pathogenic Effects in a Gestational Stage-Dependent Manner
title_fullStr Interferon Lambda Signals in Maternal Tissues to Exert Protective and Pathogenic Effects in a Gestational Stage-Dependent Manner
title_full_unstemmed Interferon Lambda Signals in Maternal Tissues to Exert Protective and Pathogenic Effects in a Gestational Stage-Dependent Manner
title_short Interferon Lambda Signals in Maternal Tissues to Exert Protective and Pathogenic Effects in a Gestational Stage-Dependent Manner
title_sort interferon lambda signals in maternal tissues to exert protective and pathogenic effects in a gestational stage-dependent manner
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9239100/
https://www.ncbi.nlm.nih.gov/pubmed/35471083
http://dx.doi.org/10.1128/mbio.03857-21
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