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Murine Skin-resident γδT Cells Impair the Immune Response to HSV in Skin

[ Vol. 20 , Issue. 3 ]

Author(s):

Marian A. Fernandez, Uet Yu, Angela L. Ferguson, Dongwei Wang, Elise Francis, Ben Roediger, Wolfgang Weninger, Laurence C. Cantrill, Anthony L. Cunningham, Stephen I. Alexander and Cheryl A. Jones *   Pages 309 - 317 ( 9 )

Abstract:


Background: HSV is an important cause of brain infection. Virus entry is often through breeches in the skin. γδT cells play an immunoprotective role in mice after corneal, genital or footpad (subcutaneous) HSV infection.

Methods: Here we report that the presence of γδT cells in murine skin is associated with increased severity of herpetic disease, reduced protective cytokine responses and increased viral spread from the skin to the sensory ganglia in the zosteriform model. γδT cell-deficient (TCR δ -/-) mice displayed significantly decreased herpetic lesion severity after flank HSV infection compared to WT C57BL/6 controls at both primary and secondary skin infection sites.

Results: Viral titer at the primary skin site was similar to WT mice in γδT cell-deficient mice, but was significantly decreased in the ganglia and secondary skin site. γδT cell-deficient mice showed increased Th1 responses by both T cells and non-T cells at the primary site, and decreased T-cell Th17 responses and immune infiltration at the secondary site.

Conclusion: Cytokine responses of epidermal and dermal γδT cells to HSV also differed in WT mice (Th1 in epidermis, and Th17 in the dermis), suggesting a functional dichotomy between these two subsets. Our data suggest that in contrast to other mouse models of HSV infection, skinresident γδT cells promote the pathogenesis of HSV in skin.

Keywords:

γδT cells, herpes simplex virus, skin inflammation, murine models, viral disease, impair.

Affiliation:

Kids Research Institute, The Children’s Hospital at Westmead, Westmead, NSW 2145, Kids Research Institute, The Children’s Hospital at Westmead, Westmead, NSW 2145, Kids Research Institute, The Children’s Hospital at Westmead, Westmead, NSW 2145, Westmead Institute for Medical Research, Westmead, NSW 2145, Kids Research Institute, The Children’s Hospital at Westmead, Westmead, NSW 2145, Sydney Medical School, The University of Sydney, Camperdown, NSW 2006, Sydney Medical School, The University of Sydney, Camperdown, NSW 2006, Kids Research Institute, The Children’s Hospital at Westmead, Westmead, NSW 2145, Sydney Medical School, The University of Sydney, Camperdown, NSW 2006, Kids Research Institute, The Children’s Hospital at Westmead, Westmead, NSW 2145, Kids Research Institute, The Children’s Hospital at Westmead, Westmead, NSW 2145



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