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


METHODS
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.
Fernandez
Sherie
S
Center For Gene Therapeutics, Department of Pathology and Molecular Medicine, Michael G. DeGroote Center for Learning and Discovery, Hamilton, Ontario, Canada.
Gillgrass
Amy
A
Kaushic
Charu
C
D000818:Animals; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D054360:Chemokine CXCL1; D019743:Chemokines, CXC / Q000378:metabolism; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006558:Herpes Genitalis / Q000378:metabolism / Q000821:virology*; D018258:Herpesvirus 2, Human; D006801:Humans; D053582:Interleukin-1alpha / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017154:Stromal Cells / Q000378:metabolism / Q000821:virology; D013997:Time Factors; D014599:Uterus / Q000378:metabolism / Q000821:virology*; D014621:Vagina / Q000378:metabolism / Q000821:virology*; D017201:Virus Shedding
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; C475895:Cxcl1 protein, mouse; D016207:Cytokines; D053582:Interleukin-1alpha; D015850:Interleukin-6; D016178:Granulocyte-Macrophage Colony-Stimulating Factor