Abstract |
The role of Fas- and TNF-receptor 1 (TNF-R1)-mediated apoptosis in the clearance of virally infected cells and in the regulation of the immune response was analyzed after murine cytomegalovirus (MCMV) infection of C57BL/6 (B6)-+/+ mice, Fas-mutant B6-lpr/lpr mice, TNF-R1 knockout B6-tnfr0/0 mice, and double-deficient B6-tnfr0/0 lpr/lpr mice. There was approximately equivalent clearance of MCMV in B6-+/+, B6-tnfr0/0, and B6-lpr/lpr mice, and by day 28 no infectious virus could be detected in the liver, kidney, lung, or peritoneal exudate. However, delayed virus clearance was observed in B6-tnfr0/0 lpr/lpr mice. An acute inflammatory response occurred in the liver, lung, and kidney of all mice, which was most severe 7 d after MCMV infection, but resolved by day 28 in B6-+/+ and B6-tnfr0/0 mice, but not in B6-lpr/lpr or B6-tnfr0/0 lpr/lpr mice. These results indicate that apoptosis mediated by either Fas or TNF-R1 is sufficient for rapid clearance of the virus. However, apoptosis induced by Fas, but not TNF-R1, is required for the downmodulation of the immune response to the virus and prevention of a chronic inflammatory reaction.
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Authors | M Fleck, E R Kern, T Zhou, J Podlech, W Wintersberger, C K Edwards 3rd, J D Mountz |
Journal | The Journal of clinical investigation
(J Clin Invest)
Vol. 102
Issue 7
Pg. 1431-43
(Oct 01 1998)
ISSN: 0021-9738 [Print] United States |
PMID | 9769336
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antigens, CD
- Receptors, Tumor Necrosis Factor
- Receptors, Tumor Necrosis Factor, Type I
- fas Receptor
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Topics |
- Animals
- Antigens, CD
(genetics, metabolism, physiology)
- Apoptosis
(physiology)
- Chronic Disease
- Cytomegalovirus Infections
(pathology, physiopathology, prevention & control)
- Female
- In Situ Nick-End Labeling
(methods)
- Kidney
(pathology)
- Liver
(pathology)
- Lung
(pathology)
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Models, Biological
- Muromegalovirus
(physiology)
- Receptors, Tumor Necrosis Factor
(genetics, metabolism, physiology)
- Receptors, Tumor Necrosis Factor, Type I
- fas Receptor
(physiology)
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