Experimental lethal infection of Leptospira interrogans in mice treated with cyclophosphamide

Abstract

After preadministration of cyclophosphamide (300 mg/kg), BALB/c mice were lethally infected with Leptospira interrogans serovar lai and a virulent strain of Leptospira interrogans serovar copenhageni, and leptospiral cells were detected in both kidneys of infected mice by indirect immunofluorescent assay. Nonpathogenic leptospirae, Leptospira biflexa serovar patoc, Leptonema illini, and an avirulent strain of L. interrogans serovar copenhageni, were not parasitic to the mice treated with cyclophosphamide. The cyclophosphamide-treated mice were protected from the homologous leptospiral infection by passive immunization with anti-leptospiral monoclonal antibody or with rabbit antiserum and by active immunization with lyophilized organisms or with protective antigen. The results of active immunization in mice treated with cyclophosphamide agreed well with those in nontreated hamsters, which were sensitive to the organisms. Furthermore, these experiments were reproducible with any lot of cyclophosphamide used. These results indicated that cyclophosphamide-treated mice can be used in the experimental infection of Leptospira in place of hamsters or guinea pigs.

Protective immunity of recombinant LipL21 and I-LipL21 against Leptospira interrogans serovar Autumnalis N2 infection

“…Due to the maintenance difficulties and supply of hamsters or guinea pigs for routine experimentation, mice, as an alternate, are being considered for leptospiral vaccines assessment and immunogenicity [10]. Since there was limited access to golden Syrian hamsters during this study, Cy mice was used as an alternate as used in previous studies [8,9,10]. In the case of non-availability of hamsters, the Cy mice could be an ideal experimental model which has been further evidenced in this study through MACS specific challenge experiments in comparison with hamsters and BALB/c mice.…”

“…Moreover, Syrian hamsters have certain limitations for the measurement of cytokine profile at the transcriptional level [26,27]. The use of Cy mice as a susceptible model was adequately validated in studies from other groups [8,9]. These studies have substantiated the usage of mice as an animal model for immunization and challenge experiments for leptospires and its products.…”

“…However, Adler and Faine [9], reported that BALB/c mice can be lethally infected with virulent Leptospira by pre-administration of cyclophosphamide (Cy), an alkylating agent that suppresses the primary humoral response of the host, at 2 days before challenge and that immunosuppressed mice treated with Cy could possibly serve as an animal model for immunization studies. Masuzawa et al, [8] further confirmed the usefulness of pre-administration Cy in mice as an experimental model of leptospiral lethal infection and compared the results of experimental infection in Cy treated mice with those in hamsters. These results indicated that Cy treated mice can be used in the experimental infection of Leptospira in place of hamsters or guinea pigs.…”

“…However, the upkeep of these animals is laborious in comparison with mice and experimental data can vary as a result of genetic heterogeneity [8]. Maintenance of hamsters/guinea pigs in a laboratory animal house is very expensive compared to mice.…”

Toll-Like Receptor 4 Protects against LethalLeptospira interrogansSerovar Icterohaemorrhagiae Infection and Contributes to In Vivo Control of Leptospiral Burden

“…Infection of mice and rats to reproduce human disease has been inconsistent, often requiring immunosuppressive treatment with drugs such as cyclophosphamide or corticosteroids (1,2,19,24). The number of organisms required to initiate infection in small-animal models varies widely for unknown reasons (7).…”