bAlthough Leptospira can infect a wide range of mammalian species, most studies have been conducted in golden Syrian hamsters, a species particularly sensitive to acute disease. Chronic disease has been well characterized in the rat, one of the natural reservoir hosts. Studies in another asymptomatic reservoir host, the mouse, have occasionally been done and have limited infection to mice younger than 6 weeks of age. We analyzed the outcome of sublethal infection of C3H/HeJ mice older than age 10 weeks with Leptospira interrogans serovar Copenhageni. Infection led to bloodstream dissemination of Leptospira, which was followed by urinary shedding, body weight loss, hypothermia, and colonization of the kidney by live spirochetes 2 weeks after infection. In addition, Leptospira dissemination triggered inflammation in the kidney but not in the liver or lung, as determined by increased levels of mRNA transcripts for the keratinocyte-derived chemokine, RANTES, macrophage inflammatory protein 2, tumor necrosis factor alpha, interleukin-1␤, inducible nitric oxide synthase, interleukin-6, and gamma interferon in kidney tissue. The acquired humoral response to Leptospira infection led to the production of IgG mainly of the IgG1 subtype. Flow cytometric analysis of splenocytes from infected mice revealed that cellular expansion was primarily due to an increase in the levels of CD4؉ and double-negative T cells (not CD8؉ cells) and that CD4 ؉ T cells acquired a CD44 high CD62L low effector phenotype not accompanied by increases in memory T cells. A mouse model for sublethal Leptospira infection allows understanding of the bacterial and host factors that lead to immune evasion, which can result in acute or chronic disease or resistance to infection (protection).

Pathogenic Leptospira sp. are spirochetal bacteria responsible for leptospirosis, an emerging worldwide zoonosis. These spirochetes are very successful pathogens that infect a wide range of hosts such as fish, reptiles, birds, marsupials, and mammals. Transmission occurs when chronically infected animals excrete live bacteria in their urine, contaminating the environment. Leptospira sp. enter their hosts through damaged skin and mucosa. Chronically infected rats and mice are asymptomatic and are considered as important reservoirs of the disease. Infected humans may develop either a flu-like, usually mild illness with or without chronic asymptotic renal colonization, or a severe acute disease with kidney, liver, and heart failure, potentially leading to death. Leptospirosis is an economic burden on society due to health-care costs related to elevated morbidity of humans and loss of animals of agricultural interest. There are no effective vaccines against leptospirosis. Leptospira sp. are difficult to genetically manipulate which delays the pace of research progress. In this review, we discuss in an historical perspective how animal models have contributed to further our knowledge of leptospirosis. Hamsters, guinea pigs, and gerbils have been instrumental to study the pathophysiology of acute lethal leptospirosis and the Leptospira sp. genes involved in virulence. Chronic renal colonization has been mostly studied using experimentally infected rats. A special emphasis will be placed on mouse models, long thought to be irrelevant since they survive lethal infection. However, mice have recently been shown to be good models of sublethal infection leading to chronic colonization. Furthermore, congenic and transgenic mice have proven essential to study how innate immune cells interact with the pathogen and to understand the role of the toll-like receptor 4, which is important to control Leptospira sp. load and disease. The use of inbred and transgenic mouse models opens up the field to the comprehensive study of immune responses to Leptospira sp. infection and subsequent pathophysiology of inflammation. It also allows for testing of drugs and vaccines in a biological system that can avail of a wealth of molecular tools that enable understanding of the mechanisms of action of protective vaccines.

The cause of Lyme disease, Borrelia burgdorferi, was discovered in 1983. A 2-tiered testing protocol was established for serodiagnosis in 1994, involving an enzyme immunoassay (EIA) or indirect fluorescence antibody, followed (if reactive) by immunoglobulin M and immunoglobulin G Western immunoblots. These assays were prepared from whole-cell cultured B. burgdorferi, lacking key in vivo expressed antigens and expressing antigens that can bind non-Borrelia antibodies. Additional drawbacks, particular to the Western immunoblot component, include low sensitivity in early infection, technical complexity, and subjective interpretation when scored by visual examination. Nevertheless, 2-tiered testing with immunoblotting remains the benchmark for evaluation of new methods or approaches. Next-generation serologic assays, prepared with recombinant proteins or synthetic peptides, and alternative testing protocols, can now overcome or circumvent many of these past drawbacks. This article describes next-generation serodiagnostic testing for Lyme disease, focusing on methods that are currently available or near-at-hand.