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Induction of indoleamine 2,3-dioxygenase in mouse lung during virus infection
Abstract:
Indoleamine 2,3-dioxygenase [indoleamine: oxygen 2,3-oxidoreductase (decyclizing)] activity in the supernatant fraction (30,000 X g, 30 min) of mouse lung homogenate increased approximately 120-fold after infection with PR8 influenza virus. Both specific and total enzyme activities started to increase linearly from the 5th day after infection, reached the highest level around the 11th day, and then gradually decreased to normal values in about 3 weeks. Other enzymes in the lung, such as certain lysosomal enzymes and monoamine oxidase, did not change significantly throughout the experiments. The time course of the increase in the enzyme activity was quite different from that of virus replication in the lung (a peak by the 3rd day and persistence until the 9th day) or that of serum antibody content (started to rise on the 9th day). Rather, it appeared to be closely related to the infiltrations of mononuclear and lymphocytic cells. When mice were exposed to a higher dose of virus and did not recuperate, the time course of the increase of the enzyme activity was essentially identical to that seen with a low concentration of virus. A maximum stimulation of the enzyme activity in the lung occurred on the 9th day after infection; the increase was approximately 100-fold. However, serum antibody content was slight and virus titer in the lung remained high.
Insights
Indoleamine 2,3-dioxygenase enzyme activity significantly increases in mouse lungs after influenza infection, peaking around 11 days. This immune response is linked to cell infiltration, not viral load.
Area of Science:
- Immunology
- Virology
- Enzymology
Background:
- Influenza virus infection triggers complex host responses in the lungs.
- Indoleamine 2,3-dioxygenase (IDO) is an enzyme involved in tryptophan metabolism and immune regulation.
- Understanding IDO's role during viral infections is crucial for developing therapeutic strategies.
Purpose of the Study:
- To investigate the changes in indoleamine 2,3-dioxygenase activity in mouse lungs following PR8 influenza virus infection.
- To correlate the kinetics of IDO activity with viral replication, host immune cell infiltration, and antibody production.
Main Methods:
- Measurement of indoleamine 2,3-dioxygenase activity in lung homogenates at various time points post-infection.
- Assessing viral titers and serum antibody levels.
- Observing lung histology for immune cell infiltration.
Main Results:
- A significant, approximately 120-fold increase in lung indoleamine 2,3-dioxygenase activity was observed post-influenza infection.
- IDO activity increased linearly from day 5, peaked around day 11, and normalized within 3 weeks.
- The enzyme activity kinetics differed from viral replication and antibody response, correlating more closely with mononuclear and lymphocytic cell infiltration.
Conclusions:
- Indoleamine 2,3-dioxygenase is markedly upregulated in the mouse lung during influenza infection.
- The induction of IDO appears to be primarily driven by inflammatory cell infiltration rather than direct viral effects.
- IDO may play a significant role in the host's immune response to influenza virus.