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Acute infection of mice with highly virulent group B streptococci as a host resistance model for immunotoxicity
D B Barnes1, J M Hardin, S B Pruett
1Department of Biological Sciences, Mississippi State University, MS 39762.
Abstract:
This report describes a unique model for immunotoxicity evaluation in mice. The model is adapted from previously described mouse models for group B streptococcus (GBS) infections in human neonates. In this disease as well as a number of human diseases caused by highly virulent pathogens, the mechanisms of innate immunity are unable to protect the host, and survival is strictly dependent on acquired immunity. Unlike other host resistance models widely used in immunotoxicity studies, the GBS model utilizes bacteria that are highly virulent for mice (LD50 = 5-17 colony forming units). GBS is not virulent for adult humans and can be safely handled with typical precautions. Acquired immunity in the GBS model is induced during a 2 week period by two injections of heat-killed GBS. The immunizing doses are the minimum which will allow survival of 80-100% of mice in response to challenge with an otherwise lethal dose of live GBS (100 bacteria). Administration of the immunotoxic agents cyclophosphamide, carrageenan, or cobra venom factor during the immunization period and/or shortly before challenge significantly suppressed host resistance. For example, the composite mortality rate for unimmunized mice was 98% and the rate for immunized mice was 8.5%. For all groups treated with cyclophosphamide (one 75 mg/kg dose 48 h before each immunization) the mean mortality was 41 +/- 18%. The consistency of the model was evaluated by repetition of several treatments in independent experiments, and the model's consistency is comparable to that of other host resistance models.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
This study presents a novel mouse model for immunotoxicity testing using virulent group B streptococcus (GBS). The model effectively assesses acquired immunity suppression by common immunotoxic agents, demonstrating high consistency.
Area of Science:
- Immunology
- Toxicology
- Microbiology
Background:
- Innate immunity often fails against highly virulent pathogens, necessitating acquired immunity for host survival.
- Existing immunotoxicity models have limitations, prompting the development of new approaches.
- Group B Streptococcus (GBS) infections in neonates highlight the critical role of acquired immunity.
Purpose of the Study:
- To develop and validate a novel mouse model for immunotoxicity evaluation.
- To assess the impact of immunotoxic agents on acquired immunity using a highly virulent pathogen.
- To establish a consistent and reliable model for studying host resistance.
Main Methods:
- Adaptation of a mouse model for group B streptococcus (GBS) infections.
- Induction of acquired immunity in mice via heat-killed GBS injections.
- Administration of immunotoxic agents (cyclophosphamide, carrageenan, cobra venom factor) during immunization and before challenge.
Main Results:
- The GBS model demonstrated high virulence (LD50 = 5-17 CFU) and effective induction of acquired immunity.
- Immunotoxic agents significantly suppressed host resistance, increasing mortality rates.
- Cyclophosphamide treatment resulted in a mean mortality of 41% in immunized mice, compared to 8.5% in untreated immunized mice.
Conclusions:
- The developed GBS mouse model is a unique and effective tool for immunotoxicity evaluation.
- The model reliably demonstrates the suppressive effects of immunotoxic agents on acquired immunity.
- The model exhibits comparable consistency to other established host resistance models.