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Macrophage immunity to influenza virus: in vitro and in vivo studies
Abstract:
Using M-TUR, a macrophage-adapted avian influenza A virus (Hav1, Nav3), antiviral resistance of peritoneal macrophages obtained from specifically or nonspecifically immunized mice towards in vitro infection was assessed. M-TUR grew to high titers in macrophages from nonimmune mice thereby causing a marked cytopathic effect. In contrast, peritoneal macrophages from mice specifically immunized with TUR virus were not affected by infection with M-TUR in vitro. This antiviral immunity was specific: mice immunized with antigenetically unrelated influenza strains such as influenza A/Hong Kong/1/68 (H3, N2) or influenza B/Lee yielded susceptible macrophages. Specific macrophage immunity could be abrogated by trypsin treatment in vitro. Susceptible macrophages from nonimmune hosts became resistant following in vitro exposure to homologous anti-TUR sera. Peritoneal exudate cells from BCG-infected animals were less susceptible to in vitro challenge with M-TUR than control macrophages. In vivo treatment of mice with the unspecific immunostimulants BCG or Corynebacterium parvum did not protect the animals against lethal infection with a hepatotropic variant of TUR.
Insights
Specific immunization confers macrophage antiviral resistance against avian influenza A virus (Hav1, Nav3). This immunity, mediated by macrophages, is specific to the TUR virus and can be abrogated by trypsin or enhanced by homologous sera.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Macrophage-adapted avian influenza A virus (M-TUR) infects macrophages from non-immune mice.
- Understanding macrophage antiviral resistance is crucial for influenza control.
Purpose of the Study:
- To assess antiviral resistance of mouse peritoneal macrophages against M-TUR.
- To determine the specificity and mechanisms of macrophage-mediated antiviral immunity.
Main Methods:
- Peritoneal macrophages from specifically or nonspecifically immunized mice were infected with M-TUR in vitro.
- Assays included cytopathic effect assessment, trypsin treatment, and exposure to anti-TUR sera.
- Macrophage susceptibility was also tested after in vivo BCG or Corynebacterium parvum treatment.
Main Results:
- Macrophages from mice specifically immunized with TUR virus resisted M-TUR infection.
- This resistance was specific, as macrophages from mice immunized with unrelated influenza strains remained susceptible.
- Trypsin treatment abrogated specific macrophage immunity, while homologous anti-TUR sera conferred resistance to susceptible macrophages.
- BCG-infected animals showed reduced susceptibility in vitro, but in vivo immunostimulation did not prevent lethal TUR infection.
Conclusions:
- Specific immunization induces potent, specific antiviral resistance in macrophages against avian influenza A virus.
- Macrophage antiviral immunity involves specific recognition and can be modulated by sera and enzymatic treatment.
- In vitro findings on macrophage resistance do not fully translate to in vivo protection against lethal influenza infection.