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Cytotoxic interactions between bovine parainfluenza type 3 virus and bovine alveolar macrophages
B M Adair1, H E Bradford, M S McNulty
1Veterinary Sciences Division, Belfast, Ireland. brian.adair@dani.gov.uk
Abstract:
This paper describes an investigation of the cytotoxic activity of bovine alveolar macrophages for parainfluenza type 3 (PI-3) virus-infected target cells, using 51Cr release assays. Alveolar macrophages from uninfected calves were shown to be capable of killing PI-3 virus infected cells without the presence of antibody or complement (antibody-independent cell-mediated cytotoxicity). The level of killing was shown to vary from animal to animal with specific lysis values ranging from <5% to 70%. Presence of PI-3 virus antiserum was shown to inhibit, rather than enhance macrophage cytotoxicity in a dose-dependent manner, suggesting that bovine alveolar macrophages do not always exhibit antibody-dependent lysis in all cases. Following intranasal and intratracheal inoculation of calves with PI-3 virus, the level of cytotoxicity by macrophages lavaged from the lungs of the calves increased substantially, and by Day 5 post inoculation, levels of 95% to 98% specific lysis were recorded. After Day 5, the killing ability decreased rapidly to low levels. Cell-free lavage fluids, collected from PI-3 virus infected and control calves at various times throughout the experiment, were incubated with aliquots of an alveolar macrophage population from an uninfected donor calf, which initially showed a low level of killing, and were subsequently added to PI-3 virus infected target cells. The recorded levels of cytotoxicity, mirrored those which were seen with the initial macrophage effector cells from the infected and control animals, suggesting that macrophage cytotoxicity was largely controlled by extracellular factors.
Insights
Bovine alveolar macrophages kill parainfluenza type 3 virus-infected cells independently of antibodies. Cytotoxicity increases after infection but is regulated by extracellular factors in lung lavage fluids.
Area of Science:
- Veterinary Immunology
- Cellular Immunology
- Virology
Background:
- Bovine alveolar macrophages play a role in lung immunity.
- Parainfluenza type 3 (PI-3) virus is a significant respiratory pathogen in cattle.
Purpose of the Study:
- To investigate the cytotoxic activity of bovine alveolar macrophages against PI-3 virus-infected cells.
- To determine the role of antibodies and extracellular factors in this cytotoxicity.
Main Methods:
- 51Cr release assays were used to measure cytotoxic activity.
- Macrophage cytotoxicity was assessed in vitro and in vivo following PI-3 virus infection in calves.
- Extracellular factors in lavage fluids were analyzed for their effect on cytotoxicity.
Main Results:
- Bovine alveolar macrophages exhibited antibody-independent cell-mediated cytotoxicity against PI-3 virus-infected cells.
- Cytotoxicity levels varied significantly between individual animals.
- PI-3 virus antiserum inhibited, rather than enhanced, macrophage cytotoxicity.
- Macrophage cytotoxicity increased substantially after PI-3 virus inoculation in vivo, peaking by Day 5.
- Extracellular factors in lung lavage fluids largely controlled macrophage cytotoxic activity.
Conclusions:
- Bovine alveolar macrophages possess intrinsic cytotoxic capabilities against PI-3 virus-infected cells.
- Antibody-dependent cytotoxicity is not consistently observed and can be inhibited by antiserum.
- Extracellular factors present in the lung environment significantly modulate macrophage cytotoxic function.