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Effect of Interferon and Interferon Inducers on Infections with a Nonviral Intracellular Microorganism, Chlamydia
J Kazar1, J D Gillmore, F B Gordon
1Department of Microbiology, Naval Medical Research Institute, Bethesda, Maryland 20014.
Abstract:
The effect of mouse interferon (IF) on the multiplication of Chlamydia trachomatis (strain MRC-1/G) in homologous (L-929) cell cultures and the effect of the IF inducers Newcastle disease virus (NDV) and polyriboinosinic acid-polyribocytidylic acid complex (poly I:C) on the experimental infection of mice with aerosolized C. trachomatis (strain MoPn) were investigated. Treatment of infected cell cultures with IF reduced the number of cells containing chlamydial inclusions and depressed the yield of chlamydiae as determined by titrations for infectivity. Growth of chlamydiae was reduced when cultures were exposed to IF 6 or 18 hr before infection, and slight reduction of the yield was also detectable in cell cultures treated with IF at early intervals (0 or 4 hr) after chlamydial infection. No effect of IF on penetration of chlamydiae into mouse cells was observed, whether phagocytic cells from peritoneal washings or L-929 cells were used, indicating that the inhibitory effect of IF occurs after chlamydiae enter the host cell. Additional evidence was obtained that a significant effect of IF occurs at an early stage in maturation of the intracellular chlamydiae. In mice exposed repeatedly to NDV aerosols and challenged with aerosolized MoPn 8 hr after the first exposure to NDV, mortality was delayed by 2 to 3 days and lung consolidation was slightly reduced at 3 days after infection. Yields of chlamydiae from lung pools of NDV-treated mice, taken at 3, 6, and 9 days after challenge, were not significantly different from those of controls. Similar results were obtained when mice were challenged with MoPn 8 hr after intranasal injection with 100 mug of poly I:C or 24 hr after intravenous injection with 200 mug of poly I:C. In contrast, administration of 0.2 ml of NDV (10(8.3) plaque-forming units) intravenously 10 hr before or 24 hr after challenge with MoPn accelerated mortality of mice by 2 to 3 days. In all experiments, detectable levels of IF in sera or 20% lung suspensions were found only up to 48 to 72 hr after exposure of mice to IF inducers.
Insights
Mouse interferon (IF) inhibits Chlamydia trachomatis growth in cell cultures by affecting intracellular maturation. IF inducers like NDV and poly I:C showed limited protective effects in vivo against chlamydial infection in mice.
Area of Science:
- Immunology
- Microbiology
- Virology
Background:
- Chlamydia trachomatis is a significant human pathogen.
- Interferon (IF) plays a crucial role in antiviral and antibacterial immunity.
- Understanding IF's role in Chlamydia infections is vital for developing therapeutic strategies.
Purpose of the Study:
- To investigate the effect of mouse interferon (IF) on Chlamydia trachomatis multiplication in cell cultures.
- To evaluate the efficacy of IF inducers, Newcastle disease virus (NDV) and poly I:C, in protecting mice against experimental Chlamydia trachomatis infection.
Main Methods:
- In vitro studies using L-929 cell cultures infected with C. trachomatis (strain MRC-1/G) and treated with IF.
- In vivo studies involving experimental infection of mice with aerosolized C. trachomatis (strain MoPn) after treatment with NDV or poly I:C.
- Assessment of chlamydial load, inclusion formation, infectivity, and mouse mortality.
Main Results:
- IF treatment significantly reduced chlamydial inclusion numbers and infectivity in cell cultures.
- IF's inhibitory effect was observed after chlamydiae entered host cells, likely during early intracellular maturation.
- NDV and poly I:C administration provided limited protection against C. trachomatis infection in mice, with no significant reduction in chlamydial yield from lungs.
- Intravenous NDV administration prior to or after challenge paradoxically accelerated mortality in mice.
Conclusions:
- Mouse interferon exhibits direct inhibitory effects on Chlamydia trachomatis intracellular growth, primarily by interfering with its maturation.
- IF inducers (NDV, poly I:C) demonstrate limited therapeutic potential against experimental Chlamydia trachomatis infection in mice.
- Further research is needed to elucidate the complex interplay between interferon, chlamydial infection, and host immune responses.
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