The mouse disease model has the advantage of a broad array of immunological and genetic tools available for basic research. Some studies on transgenic and/or mutant mouse strains as models for experimental leptospirosis have been reported; however, the wider use of such models is hampered by a poor understanding of the outcome of experimental leptospiral infection among the different mouse strains available. Here, the outcome of infection by a virulent strain of Leptospira interrogans serogroup Icterohaemorrhagiae strain Cop was studied in four commonly used wildtype mouse strains: A, CBA, BALB/c and C57BL/6. The end points evaluated in this study were survival, presence of kidney lesions, leptospiral load in kidney samples, microscopic agglutination test titre and anti-leptospiral IgG antibody levels. As expected, none of the mouse strains were susceptible to lethal leptospirosis. However, these strains developed specific pathologies associated with sublethal leptospirosis. The A and C57BL/6 strains exhibited a high leptospiral load in kidney samples and the CBA and C57BL/6 strains developed severe inflammatory lesions, whilst the BALB/c strain proved to be the most resistant to subclinical leptospirosis.
The aims of this study were to investigate the frequency of pulmonary hemorrhage (PH) in mice unable to produce functional B and T lymphocytes and to explore the effect of an inducible nitric oxide synthase gene (Inos) knockout (KO) on the frequency/severity of interstitial nephritis in vivo. We studied the outcome of infection by the virulent Leptospira interrogans serovar Copenhageni strain Cop. The animals used were Inos KO mice, recombination activating gene 1 (Rag1) KO mice, CB17 severe combined immunodeficiency (SCID) mice, and the respective wild-type (WT) C57BL/6 and BALB/c controls. The Inos KO and WT mice survived with no clinical symptoms of leptospirosis. The frequency and severity of nephritis was significantly lower in the Inos KO mice. All of the Rag1 KO and SCID animals died of acute leptospirosis, whereas all of the WT mice survived. PH was observed in 57 and 94% of Rag1 KO mice and in 83 and 100% of SCID mice, using inoculum doses of 10 7 and 10 6 leptospires, respectively. There was no evidence of PH in the WT controls. In conclusion, the loss of the Inos gene had a negligible effect on the outcome of leptospiral infection, although we observed a reduced susceptibility for interstitial nephritis in this group. Of note, the absence of functional B-and T-cell lymphocytes did not preclude the occurrence of PH. These data provide evidence that PH in leptospirosis may not be related only to autoimmune mechanisms.
In determining the efficacy of new vaccine candidates for leptospirosis, the primary end point is death and an important secondary end point is sterilizing immunity. However, evaluation of this end point is often hampered by the time-consuming demands and complexity of methods such as culture isolation (CI). In this study, we evaluated the use of an imprint (or touch preparation) method (IM) in detecting the presence of leptospires in tissues of hamsters infected with Leptospira interrogans serovar Copenhageni. In a dissemination study, compared to CI, the IM led to equal or improved detection of leptospires in kidney, liver, lung and blood samples collected post-infection and overall concordance was good (k50.61). Furthermore, in an evaluation of hamsters immunized with a recombinant leptospiral protein-based vaccine candidate and subsequently challenged, the agreement between the CI and IM was very good (k50.84). These findings indicate that the IM is a rapid method for the direct observation of Leptospira spp. that can be readily applied to evaluating infection in experimental animals and determining sterilizing immunity when screening potential vaccine candidates. INTRODUCTIONLeptospirosis is a widespread zoonosis with a global distribution, caused by pathogenic spirochaetes of the genus Leptospira (Adler & de la Pena Moctezuma, 2009;Levett, 2001). The major impact of leptospirosis is the high rate of case fatality due to its most severe complications: Weil's disease (.10 %) (Bharti et al., 2003) and severe pulmonary haemorrhage syndrome (.50 %) (Gouveia et al., 2008; Marotto et al., 1999;Park et al., 1989). A priority in current research on leptospirosis is the development of a vaccine that is able to elicit long-term immunity and to induce cross-protection against the serovars that are of greatest importance to public health (Adler & de la Pena Moctezuma, 2009;Koizumi & Watanabe, 2005;McBride et al., 2005).Several groups have reported on the use of various animal models, including mice, hamsters and gerbils, for vaccine candidate evaluation studies (Haake et al., 1999;Koizumi & Watanabe, 2004;Palaniappan et al., 2006;Silva et al., 2007; Sonrier et al., 2000). The primary goal of any vaccine is to induce a specific immune response such that the initial infection is prevented or subsequently eliminated (Seder & Mascola, 2003). Therefore, an important evaluation of vaccine efficacy is carriage status, as a successful vaccine should confer sterilizing immunity to the vaccinated animal. However, the gold standard protocol is culture isolation (CI), with the potential problems of contamination, incubator space requirements and delayed results (up to 8 weeks) (Palaniappan et al., 2005 (Jan et al., 2008;Olsen & Stenderup, 1990;Silverman & Gay, 1995). The aim of this study was to adapt and evaluate the imprint method (IM) for the direct observation of leptospires in samples from experimentally infected hamsters, comparing its performance against CI and immunohistochemistry (IHC). METHODSLeptospira strain and cultu...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.