Cargando…
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...
Autores principales: | , , |
---|---|
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 |
_version_ | 1784737215766593536 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9239100 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT casazzarebeccal interferonlambdasignalsinmaternaltissuestoexertprotectiveandpathogeniceffectsinagestationalstagedependentmanner AT philipdraket interferonlambdasignalsinmaternaltissuestoexertprotectiveandpathogeniceffectsinagestationalstagedependentmanner AT lazearhelenm interferonlambdasignalsinmaternaltissuestoexertprotectiveandpathogeniceffectsinagestationalstagedependentmanner |