Murine cytomegalovirus induces a Sjögren's syndrome-like disease in C57Bl/6-lpr/lpr mice.

Academic Article

Abstract

  • OBJECTIVE: To analyze Fas and tumor necrosis factor receptor I (TNFRI) apoptosis pathways in salivary gland inflammatory disease induced by murine cytomegalovirus (MCMV) infection. METHODS: Four different strains of mice (C57BI/6 [B6]-+/+, Fas-deficient B6-lpr/lpr, TNFRI-deficient B6-tnfr1(0/0), and B6-tnfr1(0/0)-lpr/lpr mice) were infected intraperitoneally with the Smith strain of MCMV (1 x 10(5) plaque-forming units). Viral load was determined by a plaque assay, inflammation and apoptosis by immunohistochemistry and staining with terminal dUTP nickend labeling, and autoantibodies by enzyme-linked immunosorbent assay. RESULTS: Infectious MCMV was not detectable by day 100. Although all MCMV-infected mice developed acute sialadenitis by day 28, a chronic (>100 days), severe salivary gland inflammation and anti-Ro and anti-La antibodies developed only in the B6-lpr/lpr mice. Apoptotic cells were detected during the acute, but not the chronic, phase of inflammation. CONCLUSION: Both Fas- and TNFRI-mediated apoptosis contribute to the clearance of MCMV-infected cells in the salivary glands. However, because Fas-mediated apoptosis is necessary for the down-modulation of the immune response, a defect in this process can lead to a postinfection, chronic inflammatory response that resembles Sjögren's syndrome.

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    Keywords

  • Animals, Antibody Formation, Apoptosis, Autoantibodies, Cytomegalovirus Infections, Female, Immunophenotyping, Mice, Mice, Inbred C57BL, Mice, Inbred MRL lpr, Muromegalovirus, Mutation, Receptors, Tumor Necrosis Factor, Salivary Glands, Sialadenitis, Sjogren's Syndrome, fas Receptor

    • Author List

  • Fleck M; Kern ER; Zhou T; Lang B; Mountz JD

    • Start Page

  • 2175

    • End Page

  • 2184

    • Volume

  • 41

    • Issue

  • 12