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Susceptibility of mice treated with cyclophosphamide to lethal infection with Leptospira interrogans Serovar pomona
Abstract:
Mice not normally susceptible to infection with Leptospira interrogans serovar pomona were rendered susceptible to lethal infections by treatment with a single dose of 300 mg of cyclophosphamide (Cy) per kg administered optimally from 4 days before to 1 day after infection. Cy-treated mice with either passively or actively acquired antibody were protected from death. Blood levels of leptospires in infected untreated and in Cy-treated mice remained similar until 2 days after infection, when untreated mice cleared the leptospires. Soon afterwards, opsonizing and agglutinating antibody appeared. Cy-treated mice given spleen cells from other normal or specifically immune mice were protected from infection. An important factor in the natural resistance of mice to leptospiral infection appears to be their capacity to produce circulating antibody within 48 to 72 h. Applications are suggested for this animal model in vaccination and protection studies.
Insights
Mice treated with cyclophosphamide (Cy) became susceptible to lethal Leptospira infections. Antibody production within 48–72 hours is crucial for natural resistance in mice.
Area of Science:
- Immunology
- Infectious Diseases
- Microbiology
Background:
- Mice are naturally resistant to Leptospira interrogans serovar pomona infections.
- Leptospirosis is a significant zoonotic disease with public health implications.
Purpose of the Study:
- To investigate the role of the immune system in natural resistance to Leptospira infection in mice.
- To establish a murine model for studying Leptospira infection and evaluating protective strategies.
Main Methods:
- Mice were treated with cyclophosphamide (Cy) to induce immunosuppression.
- Leptospira interrogans serovar pomona infection was administered to assess susceptibility.
- Passive and active immunization, as well as adoptive transfer of spleen cells, were employed.
Main Results:
- Cyclophosphamide treatment rendered mice susceptible to lethal Leptospira infections.
- Both passively and actively acquired antibodies protected Cy-treated mice from death.
- Untreated mice cleared leptospires within 2 days, correlating with antibody appearance.
- Spleen cell transfer conferred protection in Cy-treated infected mice.
Conclusions:
- The capacity to produce circulating antibodies within 48–72 hours is a key factor in natural mouse resistance to Leptospira.
- This study establishes a valuable animal model for Leptospira vaccination and protection research.