Murine cytomegalovirus induces a Sjögren's syndrome‐like disease in C57Bl/6‐lpr/lpr mice
M Fleck, ER Kern, T Zhou, B Lang… - Arthritis & …, 1998 - Wiley Online Library
M Fleck, ER Kern, T Zhou, B Lang, JD Mountz
Arthritis & Rheumatism, 1998•Wiley Online LibraryObjective 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 (C57Bl/6 [B6]-+/+, Fas-deficient B6-lpr/lpr,
TNFRI-deficient B6-tnfr1 0/0, and B6-tnfr1 0/0-lpr/lprmice) were infected intraperitoneally
with the Smith strain of MCMV (1× 10 5 plaque-forming units). Viral load was determined by
a plaque assay, inflammation and apoptosis by immunohistochemistry and staining with …
in salivary gland inflammatory disease induced by murine cytomegalovirus (MCMV)
infection. Methods Four different strains of mice (C57Bl/6 [B6]-+/+, Fas-deficient B6-lpr/lpr,
TNFRI-deficient B6-tnfr1 0/0, and B6-tnfr1 0/0-lpr/lprmice) were infected intraperitoneally
with the Smith strain of MCMV (1× 10 5 plaque-forming units). Viral load was determined by
a plaque assay, inflammation and apoptosis by immunohistochemistry and staining with …
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 (C57Bl/6 [B6]-+/+, Fas-deficient B6-lpr/lpr, TNFRI-deficient B6-tnfr1 0/0, and B6-tnfr1 0/0-lpr/lprmice) were infected intraperitoneally with the Smith strain of MCMV (1× 10 5 plaque-forming units). Viral load was determined by a plaque assay, inflammation and apoptosis by immunohistochemistry and staining with terminal dUTP nick-end 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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