Viral infection of the ovaries compromises pregnancy and reveals innate immune mechanisms protecting fertility

Tomac, Jelena; Mazor, Marija; Lisnić, Berislav; Golemac, Mijo; Kveštak, Daria; Bralić, Marina; Zulle, Lidija Bilić; Brinkmann, Melanie M.; Dölken, Lars; Reinert, Line S.; Paludan, Søren R.; Krmpotić, Astrid; Jonjić, Stipan; Lisnić, Vanda Juranić

doi:10.1016/j.immuni.2021.04.020

Cited by 8 publications

(4 citation statements)

References 84 publications

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“…Inflammatory responses during congenital CMV infection involve the activation of immune cells and the expression of various proinflammatory cytokines [ 10 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. Traditionally, pivotal players like IFNγ and TNFα have been the focus of antiviral defense [ 14 , 20 , 60 , 61 , 62 ].…”

Section: Discussionmentioning

confidence: 99%

“…A significant challenge in unraveling the pathogenesis of HCMV infection lies in its strict species specificity, confining investigations to animal models [ 8 ]. The mouse CMV (MCMV) is a pivotal model in HCMV research, offering valuable insights into various facets of HCMV disease [ 8 , 9 , 10 , 11 ]. One drawback of the mouse model is that, unlike HCMV, MCMV does not cross the placenta.…”

Section: Introductionmentioning

confidence: 99%

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Comprehensive Analysis of Soluble Mediator Profiles in Congenital CMV Infection Using an MCMV Model

Karner,

Kvestak,

Lisnic

et al. 2024

Viruses

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Congenital human cytomegalovirus (HCMV) infection may cause life-threatening disease and permanent damage to the central nervous system. The mouse model of CMV infection is most commonly used to study mechanisms of infection and pathogenesis. While essential to limit mouse CMV (MCMV) replication, the inflammatory responses, particularly IFNγ and TNFα, cause neurodevelopmental abnormalities. Other soluble mediators of the immune response in most tissues remain largely unexplored. To address this gap, we quantified 48 soluble mediators of the immune response, including 32 cytokines, 10 chemokines, 3 growth factors/regulators, and 3 soluble receptors in the spleen, liver, lungs, and brain at 9 and 14 days postinfection (dpi). Our analysis found 25 induced molecules in the brain at 9 dpi, with an additional 8 showing statistically elevated responses at 14 dpi. Specifically, all analyzed CCL group cytokines (CCL2, CCL3, CCL4, CCL5, CCL7, and CCL11) were upregulated at 14 dpi in the brain. Furthermore, data revealed differentially regulated analytes across tissues, such as CCL11, CXCL5, and IL-10 in the brain, IL-33/IL-33R in the liver, and VEGF-a and IL-5 in the lungs. Overall, this study provides an overview of the immune dynamics of soluble mediators in congenital CMV.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comprehensive Analysis of Soluble Mediator Profiles in Congenital CMV Infection Using an MCMV Model

Karner,

Kvestak,

Lisnic

et al. 2024

Viruses

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“…Here, we observed that EHDV-8 replicated at high levels in the female genital tract. Considering that viral infection of the ovaries compromises pregnancy 78 , 79 , the IFNAR(-/-) mouse model could shed light on the underlying mechanisms of this phenomenon. This model also provided new insights into oral transmission of BTV 80 , even though evidence of horizontal transmission of BTV existed 81 .…”

Section: Discussionmentioning

confidence: 99%

IFNAR(-/-) Mice Constitute a Suitable Animal Model for Epizootic Hemorrhagic Disease Virus Study and Vaccine Evaluation

Jiménez-Cabello,

Utrilla-Trigo,

Benavides-Silván

et al. 2024

Int. J. Biol. Sci.

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Epizootic hemorrhagic disease (EHD), caused by Epizootic hemorrhagic disease virus (EHDV), is an emerging and severe livestock disease. Recent incursion and distribution of EHDV in Europe have outlined the emerging character of EHD. Despite its worldwide impact, numerous knowledge gaps exist. A range of inconveniences restricts utilization of natural hosts of EHDV. Here, we show that adult mice deficient in type I IFN receptor (IFNAR(-/-)) are highly susceptible to EHDV-6 and EHDV-8 infection when the virus is administered subcutaneously. Disease was characterized by ruffled hair, reluctance to move, dehydration and conjunctivitis, with viraemia detected from day 5 post-infection. A deeper characterization of EHDV-8 infection showed viral replication in the lung, liver, spleen, kidney, testis and ovaries. Importantly, increased expression levels of pro-inflammatory cytokines IL-1β, IL-6 and CXCL2 were observed in spleen after EHDV-8 infection. Furthermore, IFNAR(-/-) adult mice immunized with a EHDV-8 inactivated vaccine elicited neutralizing antibodies specific of EHDV-8 and full protection against challenge with a lethal dose of this virus. This study also explores the possibilities of this animal model for study of BTV and EHDV coinfection. In summary, the IFNAR(-/-) mouse model faithfully recapitulates EHD and can be applied for vaccine testing, which can facilitate progress in addressing the animal health challenge posed by this virus.

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“…Innate immune antiviral response plays a crucial role in the response. In cytomegalovirus infection, Tomac and coworkers [88] were able to show that low viral load and high viral load affect the corpus luteum differently in a murine model. There is local inflammatory activation at low viral load, but pregnancy continues; there is a massive immune response at high viral load, leading to pregnancy loss.…”

Section: Nk Cells In Infectious Diseases In Pregnancymentioning

confidence: 99%

A Brief Analysis of Tissue-Resident NK Cells in Pregnancy and Endometrial Diseases: The Importance of Pharmacologic Modulation

Garmendia

Sanctis

2021

Immuno

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NK cells are lymphocytes involved in the innate and adaptative immune response. These cells are located in peripheral blood and tissues with ample functions, from immune vigilant to tolerogenic reactions. In the endometrium, NK cell populations vary depending on age, hormones, and inflammation. When pregnancy occurs, tissue-resident NK cells and conventional NK cells are recruited to protect the fetus, a tolerogenic response. On the contrary, in the inflamed endometrium, various inflammatory cells down-regulate NK tolerance and impair embryo implantation. Therefore, NK cells’ pharmacological modulation is difficult to achieve. Several strategies have been used, from progesterone, lipid emulsions to steroids; the success has not been as expected. However, new therapeutic approaches have been proposed to decrease the endometrial inflammatory burden and increase pregnancy success based on understanding NK cell physiology.

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Viral infection of the ovaries compromises pregnancy and reveals innate immune mechanisms protecting fertility

Cited by 8 publications

References 84 publications

Comprehensive Analysis of Soluble Mediator Profiles in Congenital CMV Infection Using an MCMV Model

Comprehensive Analysis of Soluble Mediator Profiles in Congenital CMV Infection Using an MCMV Model

IFNAR(-/-) Mice Constitute a Suitable Animal Model for Epizootic Hemorrhagic Disease Virus Study and Vaccine Evaluation

A Brief Analysis of Tissue-Resident NK Cells in Pregnancy and Endometrial Diseases: The Importance of Pharmacologic Modulation

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