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Animal Models of Leptospirosis: Of Mice and Hamsters
#MMPMID28270811
Gomes-Solecki M
; Santecchia I
; Werts C
Front Immunol
2017[]; 8
(?): 58
PMID28270811
show ga
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.
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