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

Authors

  • Sherie Fernandez,

    1. Center For Gene Therapeutics, Department of Pathology and Molecular Medicine, Michael G. DeGroote Center for Learning and Discovery, Hamilton, Ontario, Canada;
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  • Amy Gillgrass,

    1. Center For Gene Therapeutics, Department of Pathology and Molecular Medicine, Michael G. DeGroote Center for Learning and Discovery, Hamilton, Ontario, Canada;
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  • Charu Kaushic

    1. Center For Gene Therapeutics, Department of Pathology and Molecular Medicine, Michael G. DeGroote Center for Learning and Discovery, Hamilton, Ontario, Canada;
    2. Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada
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Dr Charu Kaushic, Department of Pathology, MDCL 4014, McMaster University, 1200 Main Street West, Hamilton, Ontario, Canada L8P 3Z5.
E-mail: kaushic@mcmaster.ca

Abstract

Problem

This study was undertaken to evaluate the susceptibility of upper and lower reproductive tract epithelial cells (ECs) to herpes simplex virus type 2 (HSV-2) infection and examine their cytokine secretion patterns prior to and following infection.

Method of study

Primary EC cultures, grown from murine vaginal and uterine tissue, were inoculated with HSV-2. Viral shedding was measured in apical and basolateral compartments. Multi-analyte bead-based immunoassays run on Luminex, were used to analyse cytokine profiles.

Results

Both vaginal and uterine ECs became productively infected with HSV-2, ex-vivo. Uterine ECs displayed varying degrees of infection, dependent on transepithelial resistance of the monolayers. Co-culturing stromal cells did not significantly change levels of viral shedding from ECs. Uterine ECs and epithelial-stromal co-cultures constitutively secreted interleukin (IL)-1α, IL-6, mouse homologue of human IL-8 (KC) and monocyte chemotactic protein-1 (MCP-1), while vaginal epithelial-stromal co-cultures secreted granulocyte–macrophage colony stimulating factor (GM-CSF) and KC. Following exposure to HSV-2, IL-6 and MCP-1 levels decreased in uterine EC cultures.

Conclusions

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.

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