Differential Responses of Murine Vaginal and Uterine Epithelial Cells Prior to and Following Herpes Simplex Virus Type 2 (HSV‐2) Infection

Fernandez, Sherie; Gillgrass, Amy; Kaushic, Charu

doi:10.1111/j.1600-0897.2007.00482.x

Cited by 13 publications

(5 citation statements)

References 30 publications

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“…Transfer of maternally produced antibodies and cytokines across the placenta and/or exposure of the fetus to inflammatory molecules produced by the placenta and decidua in relation to viral shedding may lead to fetal brain inflammation. HSV-2 shedding has been reported to occur simultaneously in distinct regions of the genital tract, independently of lesions linked to more localized inflammation ( 46 – 48 ), and is associated with increased levels of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) ( 49 , 50 ). There is evidence that these cytokines can enter fetal circulation ( 51 – 54 ), cross the blood-brain barrier (BBB), and stimulate production of inflammatory cytokines by microglial cells and astrocytes in fetal brain, further increasing the permeability of the BBB and damaging the developing white matter ( 55 – 57 ).…”

Section: Discussionmentioning

confidence: 99%

Maternal Immunoreactivity to Herpes Simplex Virus 2 and Risk of Autism Spectrum Disorder in Male Offspring

Mahic

Mjaaland

Bøvelstad

et al. 2017

mSphere

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Maternal infections during pregnancy are associated with risk of neurodevelopmental disorders, including autism spectrum disorders (ASDs). Proposed pathogenetic mechanisms include fetal infection, placental inflammation, and maternal cytokines or antibodies that cross the placenta. The Autism Birth Cohort comprises mothers, fathers, and offspring recruited in Norway in 1999 to 2008. Through questionnaire screening, referrals, and linkages to a national patient registry, 442 mothers of children with ASD were identified, and 464 frequency-matched controls were selected. Immunoglobulin G (IgG) antibodies to Toxoplasma gondii, rubella virus, cytomegalovirus (CMV), herpes simplex virus 1 (HSV-1), and HSV-2 in plasma collected at midpregnancy and after delivery were measured by multiplexed immunoassays. High levels of HSV-2 IgG antibodies in maternal midpregnancy plasma were associated with increased risk of ASD in male offspring (an increase in HSV-2 IgG levels from 240 to 640 arbitrary units/ml was associated with an odds ratio of 2.07; 95% confidence interval, 1.06 to 4.06; P ϭ 0.03) when adjusted for parity and child's birth year. No association was found between ASD and the presence of IgG antibodies to Toxoplasma gondii, rubella virus, CMV, or HSV-1. Additional studies are needed to test for replicability of risk and specificity of the sex effect and to examine risk associated with other infections. IMPORTANCEThe cause (or causes) of most cases of autism spectrum disorder is unknown. Evidence from epidemiological studies and work in animal models of neurodevelopmental disorders suggest that both genetic and environmental factors may be implicated. The latter include gestational infection and immune activation. In our cohort, high levels of antibodies to herpes simplex virus 2 at midpregnancy were associated with an elevated risk of autism spectrum disorder in male offspring. These findings provide support for the hypothesis that gestational infection may contribute to the pathogenesis of autism spectrum disorder and have the potential to drive new efforts to monitor women more closely for cryptic gestational infection and to implement suppressive therapy during pregnancy.KEYWORDS autism, birth cohort, herpes simplex virus, infection, prenatal, serology

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Section: Discussionmentioning

confidence: 99%

Maternal Immunoreactivity to Herpes Simplex Virus 2 and Risk of Autism Spectrum Disorder in Male Offspring

Mahic

Mjaaland

Bøvelstad

et al. 2017

mSphere

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“…Several studies have shown that HSV [40] and HIV [36] are associated with an increased risk of BV, but human papillomavirus (HPV) is not similarly associated [41]. After infection with HSV, cultured uterine epithelial cells secreted lower IL-6 and MCP-1 levels [42], and cervical epithelial cells secreted less SLPI [43]. HIV has well described effects on CD4 + T cells and adaptive immunity, but has also been associated with alterations in innate mucosal immunity.…”

Section: Viral Coinfectionsmentioning

confidence: 99%

The Interplay of Host Immunity, Environment and the Risk of Bacterial Vaginosis and Associated Reproductive Health Outcomes

Murphy

Mitchell

2016

J Infect Dis.

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Bacterial vaginosis (BV) is one of the most common causes of vaginal symptoms in US women, but its causal mechanism has not yet been defined. BV is more prevalent in women who are immunosuppressed, and several risk factors for the development of BV are associated with lower quantities of immune mediators in vaginal fluid. In contrast, the poor reproductive health outcomes associated with BV, such as preterm birth and human immunodeficiency virus type 1 acquisition, are associated with increased levels of proinflammatory immune mediators in the genital tract. In this article, we discuss how variations in the host immune profile and environmental effects on host immunity may influence the risk of BV, as well as the risk of complications associated with BV.

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“…CXCL1 is produced by epithelial cells within the genital mucosa (17) and is rapidly secreted following HSV-2 infection (59). Like CXCL1, CCL2 is also generated rapidly in response to HSV-2 (59) and is associated with inflammation and tissue pathology (12,31,43).…”

Section: Discussionmentioning

confidence: 99%

Loss of the Type I Interferon Pathway Increases Vulnerability of Mice to Genital Herpes Simplex Virus 2 Infection

Conrady

Halford

Carr

2011

J Virol

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The mouse model of genital herpes relies on medoxyprogesterone treatment of female mice to render the vaginal lumen susceptible to inoculation with herpes simplex virus 2 (HSV-2). In the present study, we report that mice deficient in the A1 chain of the type I interferon receptor (CD118 ؊/؊ ) are susceptible to HSV-2 in the absence of medroxyprogesterone preconditioning. In the absence of hormone pretreatment, 2,000 PFU of a clinical isolate of HSV-2 was sufficient to establish a productive infection in the vagina of 75% ؎ 17% and in the spinal cord of 71% ؎ 14% of CD118 ؊/؊ mice, whereas the same dose of HSV-2 replicated to detectable levels in only 13% ؎ 13% of vaginal samples and 0% of spinal cord samples from wild-type mice, as determined at day 5 postinfection. The susceptibility to HSV-2 infection in the CD118 ؊/؊ mice was associated with a significant reduction in the infiltration of HSV-specific cytotoxic T lymphocytes into the vaginal tissue, the local production of gamma interferon (IFN-␥), and the expression of T cell-recruiting chemokines CCL5, CXCL9, and CXCL10. Collectively, the results underscore the significant contribution of type I IFNs in resistance to genital HSV-2 infection.

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Differential Responses of Murine Vaginal and Uterine Epithelial Cells Prior to and Following Herpes Simplex Virus Type 2 (HSV‐2) Infection

Abstract: This data shows that ECs from the upper and lower reproductive tract have different cytokine secretion profiles and respond differentially to infection. HSV-2 may be able to suppress epithelial cytokine secretion as a strategy to evade host immune system.

Cited by 13 publications

References 30 publications

Maternal Immunoreactivity to Herpes Simplex Virus 2 and Risk of Autism Spectrum Disorder in Male Offspring

Maternal Immunoreactivity to Herpes Simplex Virus 2 and Risk of Autism Spectrum Disorder in Male Offspring

The Interplay of Host Immunity, Environment and the Risk of Bacterial Vaginosis and Associated Reproductive Health Outcomes

Loss of the Type I Interferon Pathway Increases Vulnerability of Mice to Genital Herpes Simplex Virus 2 Infection

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