Differential responses of murine vaginal and uterine epithelial cells prior to and following herpes simplex virus type 2 (HSV-2) infection

Am J Reprod Immunol. 2007 May;57(5):367-77. doi: 10.1111/j.1600-0897.2007.00482.x.

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)-1alpha, 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Chemokine CCL2 / metabolism
  • Chemokine CXCL1
  • Chemokines, CXC / metabolism
  • Coculture Techniques
  • Cytokines / metabolism*
  • Epithelial Cells / metabolism
  • Epithelial Cells / virology*
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Herpes Genitalis / metabolism
  • Herpes Genitalis / virology*
  • Herpesvirus 2, Human*
  • Humans
  • Interleukin-1alpha / metabolism
  • Interleukin-6 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Stromal Cells / metabolism
  • Stromal Cells / virology
  • Time Factors
  • Uterus / metabolism
  • Uterus / virology*
  • Vagina / metabolism
  • Vagina / virology*
  • Virus Shedding

Substances

  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Chemokine CXCL1
  • Chemokines, CXC
  • Cxcl1 protein, mouse
  • Cytokines
  • Interleukin-1alpha
  • Interleukin-6
  • Granulocyte-Macrophage Colony-Stimulating Factor