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Imaging Cell Interaction in Tracheal Mucosa During Influenza Virus Infection Using Two-photon Intravital Microscopy
Published on: August 17, 2018
Interaction of influenza virus with mouse macrophages
Abstract:
Mouse peritoneal and alveolar macrophages differed substantially in their response to influenza in vitro. Immunofluorescent and infectious-center techniques showed that viral proteins were produced in only a small subpopulation (17%) of peritoneal macrophages and that these infected cells were removed from culture by 3 days postinfection. In contrast, alveolar macrophages were highly susceptible to influenza, and viral antigens were produced in all cells. This was accompanied by a cytopathic effect and cell death. However, no infectious virus was released and the infection was considered abortive. With mouse cytomegalovirus, however, both alveolar and peritoneal macrophages were equally restrictive, and viral antigens were produced in only 1 to 5% of either cell population. No significant differences were observed between mouse-virulent and -avirulent strains of influenza in their interaction with macrophages either in vitro or in vivo. In vivo, both strains induced an influx of cells to the alveolar spaces by 3 to 4 days postinfection, and this was reflected by a 5- to 10-fold increase in the number of "macrophages" in harvest fluids at this time. Many of these cells had an altered morphology compared with alveolar macrophages from uninfected mice, and the cell population as a whole was not susceptible to influenza. However, this resistance was lost by 7 days of in vitro culture.
Insights
Mouse macrophages show varied responses to influenza virus. Alveolar macrophages are susceptible, leading to abortive infections, while peritoneal macrophages show limited viral protein production and clearance.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Macrophages play a crucial role in the innate immune response to viral infections.
- Different macrophage populations, such as peritoneal and alveolar macrophages, may exhibit distinct functional characteristics.
- Understanding macrophage-pathogen interactions is vital for developing effective antiviral strategies.
Purpose of the Study:
- To investigate and compare the in vitro and in vivo responses of mouse peritoneal and alveolar macrophages to influenza virus infection.
- To examine the susceptibility of these macrophage populations to other viruses, such as mouse cytomegalovirus.
- To assess the impact of influenza virus virulence on macrophage interactions.
Main Methods:
- In vitro culture of mouse peritoneal and alveolar macrophages.
- Immunofluorescent and infectious-center assays to detect viral protein production and infectious virus.
- In vivo studies involving intranasal inoculation of mice with influenza virus.
- Analysis of bronchoalveolar lavage fluid for cellular composition and morphology.
Main Results:
- Peritoneal macrophages supported limited viral protein production (17%) and were cleared from culture within 3 days.
- Alveolar macrophages were highly susceptible to influenza, exhibiting viral antigen production in all cells, cytopathic effects, and cell death, but produced no infectious virus (abortive infection).
- Both macrophage types were restrictive to mouse cytomegalovirus, with only 1-5% showing viral antigen production.
- In vivo, influenza infection induced an influx of resistant cells to alveolar spaces, which lost resistance upon 7-day in vitro culture.
Conclusions:
- Mouse peritoneal and alveolar macrophages exhibit differential susceptibility and responses to influenza virus in vitro.
- Alveolar macrophages mount an abortive influenza infection characterized by cell death but no infectious virus release.
- In vivo, influenza infection elicits a transient influx of resistant cells in the lungs, highlighting the dynamic nature of macrophage responses during infection.
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