Abstract

Leprosy (also known as Hansen’s disease) is an infectious peripheral neurological disorder caused by Mycobacterium leprae that even today leaves millions of individuals worldwide with life-long disabilities. The specific mechanisms by which this bacterium induces nerve injury remain largely unknown, mainly owing to ethical and practical limitations in obtaining affected human nerve samples. In addition to humans, nine-banded armadillos (Dasypus novemcinctus) are the only other natural host of M. leprae, and they develop a systemically disseminated disease with extensive neurological involvement. M. leprae is an obligate intracellular parasite that cannot be cultivated in vitro. Because of the heavy burdens of bacilli they harbor, nine-banded armadillos have become the organism of choice for propagating large quantities of M. leprae, and they are now advancing as models of leprosy pathogenesis and nerve damage. Although armadillos are exotic laboratory animals, the recently completed whole genome sequence for this animal is enabling researchers to undertake more sophisticated molecular studies and to develop armadillo-specific reagents. These advances will facilitate the use of armadillos in piloting new therapies and diagnostic regimens, and will provide new insights into the oldest known infectious neurodegenerative disorder.

Highlights

  • Nerve damage is the hallmark of leprosy

  • Knowledge gained about the pathogenesis and prevention of nerve injury in leprosy might be translatable to the study of other neurodegenerative diseases. In this Review, we briefly summarize some of the unique aspects of the armadillo that are relevant for modeling leprosy, especially with respect to neurodegeneration

  • A survey of Tolllike receptor (TLR) polymorphism in armadillos found that a nonsynonymous polymorphism [A1879G (R627G) in TLR1] was significantly associated with resistance to leprosy (R.S., unpublished data)

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Summary

Introduction

Nerve damage is the hallmark of leprosy. Diagnosis of the disease is based on clinical findings of anesthetic skin lesions or evidence of nerve damage in conjunction with the presence of Mycobacterium leprae. M. leprae manifests in armadillos as a systemically disseminated infection with similar structural and pathological changes as observed in tissues and nerves of humans with leprosy. As described below, infected armadillos closely recapitulate human leprosy, and they are useful models for dissecting the underlying mechanisms of nerve damage and testing new therapeutic interventions. Recent studies indicate that M. leprae can be transmitted zoonotically between humans and wild armadillos in the southern United States (Truman et al, 2011), and biomarkers of M. leprae infection have been reported among wild armadillos in Brazil, Colombia and Argentina (Truman, 2005; Truman and Fine, 2010) This exotic-looking house-cat-sized animal is found only in the Americas and ranges from northern Argentina to the central United States. A small plastic trash can with shredded paper functions as a sham burrow and enriches the environment

Leprosy in armadillos Susceptibility and natural infection
Clinical manifestation
Immunology and histopathology
Ankle Knee
Genomic diversity and disease susceptibility
Gene expression
Findings
Conclusions and future prospects
Full Text
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