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Parasitology. 2018 Apr;145(4):443-452. doi: 10.1017/S003118201700169X. Epub 2017 Nov 8.

Dermotropic Leishmania donovani in Sri Lanka: visceralizing potential in clinical and preclinical studies.

Author information

1
Department of Parasitology,Faculty of Medicine,University of Colombo,No. 25,Kynsey Road,Colombo 8,Sri Lanka.
2
JH-Institute of Molecular Medicine,Jamia Hamdard,New Delhi,India.
3
Central Drug Research Institute,Sector 10,Jankipuram Extension,Sitapur Road,Lucknow,Uttar Pradesh 226031,India.
4
Department of Clinical Medicine, Faculty of Medicine,University of Colombo,No. 25,Kynsey Road,Colombo 8,Sri Lanka.
5
Laboratory of Emerging Pathogens,Division of Emerging and Transfusion Transmitted Diseases,Center for Biologics Evaluation and Research,Food and Drug Administration,Silver Spring, MD,USA.

Abstract

The visceralizing potential of apparently dermotropic Leishmania donovani in Sri Lanka (L. donovani-SL) was investigated through long-term follow-up of cutaneous leishmaniasis (CL) patients and in vivo and in vitro experimental infection models. CL patients (n = 250) treated effectively with intra-lesional antimony therapy were followed-up six monthly for 4 years. There was no clinical evidence of visceralization of infection (VL) during this period. Infection of BALB/c mice with L. donovani-SL (test) through intra-dermal route led to the development of cutaneous lesions at the site of inoculation with no signs of systemic dissemination, in contrast to the observations made in animals similarly infected with a visceralizing strain of L. donovani-1S (control). Cytokine (IL-10, IFN-γ) release patterns of splenocytes and lymph node cell cultures derived from mice primed with experimental infections (with either test or control parasites) revealed significantly high IFN-γ response associated with test mice with CL, while prominent IL-10 levels were observed in association with control mice with VL. Furthermore, diminished infection efficiency, intracellular growth and survival of L. donovani-SL parasites compared with L. donovani-1S were evident through in vitro macrophage infection experiments. These studies confirm, for the first time, the essential dermotropic nature of L. donovani-SL suggesting natural attenuation of virulence of local parasite strains.

KEYWORDS:

Leishmaniasis; animal models; cytokines; patient follow-up; skin lesions; virulence

PMID:
29113609
PMCID:
PMC5989320
DOI:
10.1017/S003118201700169X
[Indexed for MEDLINE]
Free PMC Article

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