Apoptosis mediated by Fas but not tumor necrosis factor receptor 1 prevents chronic disease in mice infected with murine cytomegalovirus.

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.

• 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.)

Chemical References

• Antigens, CD
• Receptors, Tumor Necrosis Factor
• Receptors, Tumor Necrosis Factor, Type I
• fas Receptor

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)