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Dissection of Adult Mouse Utricle and Adenovirus-mediated Supporting-cell Infection
Published on: March 28, 2012
Fas activity mediates airway inflammation during mouse adenovirus type 1 respiratory infection
Laura J Adkins1, Caitlyn T Molloy1, Jason B Weinberg2
1Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI, United States.
Abstract:
CD8 T cells play a key role in clearance of mouse adenovirus type 1 (MAV-1) from the lung and contribute to virus-induced airway inflammation. We tested the hypothesis that interactions between Fas ligand (FasL) and Fas mediate the antiviral and proinflammatory effects of CD8 T cells. FasL and Fas expression were increased in the lungs of C57BL/6 (B6) mice during MAV-1 respiratory infection. Viral replication and weight loss were similar in B6 and Fas-deficient (lpr) mice. Histological evidence of pulmonary inflammation was similar in B6 and lpr mice, but lung mRNA levels and airway proinflammatory cytokine concentrations were lower in MAV-1-infected lpr mice compared to infected B6 mice. Virus-induced apoptosis in lungs was not affected by Fas deficiency. Our results suggest that the proinflammatory effects of CD8 T cells during MAV-1 infection are mediated in part by Fas activation and are distinct from CD8 T cell antiviral functions.
Insights
CD8 T cells help clear mouse adenovirus type 1 (MAV-1) and cause inflammation. Fas ligand (FasL) and Fas interactions partly mediate inflammation, but not viral clearance, by CD8 T cells.
Area of Science:
- Immunology
- Virology
- Respiratory Medicine
Background:
- CD8 T cells are crucial for controlling MAV-1 infection in the lungs.
- CD8 T cell functions include viral clearance and inducing airway inflammation.
- The role of Fas ligand (FasL)/Fas interactions in these CD8 T cell functions is unclear.
Purpose of the Study:
- To investigate if FasL/Fas interactions mediate the antiviral and proinflammatory effects of CD8 T cells during MAV-1 infection.
Main Methods:
- Compared MAV-1 infected C57BL/6 (B6) mice with Fas-deficient (lpr) mice.
- Assessed viral replication, weight loss, pulmonary inflammation (histology), and cytokine levels.
- Measured FasL and Fas expression in lung tissue.
Main Results:
- Viral replication and weight loss were similar in B6 and lpr mice.
- Pulmonary inflammation histology was similar, but MAV-1-infected lpr mice had lower lung mRNA and airway cytokine levels.
- Fas deficiency did not affect virus-induced apoptosis in the lungs.
Conclusions:
- FasL/Fas interactions contribute to CD8 T cell-mediated inflammation during MAV-1 infection.
- These interactions are distinct from CD8 T cell antiviral functions.
- CD8 T cell proinflammatory effects are partly mediated by Fas activation.
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