T cell-dependent and -independent pathways to tissue destruction following herpes simplex virus-1 infection.
Viral infections can trigger tissue destruction through innate and/or adaptive immune mechanisms. Here we show that these pathways can be differentially activated after infection by different strains of the herpes simplex virus-1 (HSV-1) virus. Infection of murine corneal tissue by HSV-1 (KOS) triggers an autoreactive clone of CD4 cells that is cross-reactive with an HSV-1 epitope to initiate corneal destruction. In contrast, ocular infection by the HSV-1 (RE) strain induces murine corneal destruction through direct, T cell-independent, activation of the innate immune system. Although the relative role of these two pathways to blindness following clinical HSV-1 ocular infection is unknown, this analysis suggests a general experimental approach to evaluate the relative contribution of adaptive and innate immune mechanisms to virally induced host tissue destruction.
Huster
Katharina M
KM
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Pathology, Harvard Medical School, Boston, USA.
Panoutsakopoulou
Vily
V
Prince
Kenya
K
Sanchirico
Marie E
ME
Cantor
Harvey
H
D000818:Animals; D015551:Autoimmunity; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D018259:Herpesvirus 1, Human / Q000472:pathogenicity; D007108:Immune Tolerance; D016849:Keratitis, Herpetic / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology*
D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; D011948:Receptors, Antigen, T-Cell; C064655:V(D)J recombination activating protein 2