title: Animal Models of Leptospirosis: Of Mice and Hamsters.
abstract: PathogenicLeptospirasp. 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.Leptospirasp. 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.Leptospirasp. 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 theLeptospirasp. 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 controlLeptospirasp. load and disease. The use of inbred and transgenic mouse models opens up the field to the comprehensive study of immune responses toLeptospirasp. 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.
authors.affiliation: Department of Microbiology, Immunology and Biochemistry, The University of Tennessee Health Science Center , Memphis, TN , USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Gomes-Solecki
authors.affiliation: Institut Pasteur, Unité Biologie et Génétique de la Paroi Bactérienne, Paris, France; INSERM, équipe Avenir, Paris, France.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Santecchia
authors.affiliation: Institut Pasteur, Unité Biologie et Génétique de la Paroi Bactérienne, Paris, France; INSERM, équipe Avenir, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Werts
keywords: Leptospira interrogans; TLR2; TLR4; animal models; hamsters; leptospirosis; mouse models; virulence factors