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Science 331 (6018): 775-778

Copyright © 2011 by the American Association for the Advancement of Science

Leishmania RNA Virus Controls the Severity of Mucocutaneous Leishmaniasis

Annette Ives,1 Catherine Ronet,1 Florence Prevel,1 Giulia Ruzzante,1 Silvia Fuertes-Marraco,1 Frederic Schutz,2 Haroun Zangger,1 Melanie Revaz-Breton,1,* Lon-Fye Lye,3 Suzanne M. Hickerson,3 Stephen M. Beverley,3 Hans Acha-Orbea,1 Pascal Launois,4 Nicolas Fasel,1,{dagger} Slavica Masina1

Abstract: Mucocutaneous leishmaniasis is caused by infections with intracellular parasites of the Leishmania Viannia subgenus, including Leishmania guyanensis. The pathology develops after parasite dissemination to nasopharyngeal tissues, where destructive metastatic lesions form with chronic inflammation. Currently, the mechanisms involved in lesion development are poorly understood. Here we show that metastasizing parasites have a high Leishmania RNA virus–1 (LRV1) burden that is recognized by the host Toll-like receptor 3 (TLR3) to induce proinflammatory cytokines and chemokines. Paradoxically, these TLR3-mediated immune responses rendered mice more susceptible to infection, and the animals developed an increased footpad swelling and parasitemia. Thus, LRV1 in the metastasizing parasites subverted the host immune response to Leishmania and promoted parasite persistence.

1 Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland.
2 Swiss Institute of Bioinformatics, University of Lausanne, 1015 Dorigny, Switzerland.
3 Department of Molecular Microbiology, Washington University, School of Medicine, St Louis, MO 63110, USA.
4 World Health Organization–Immunology Research and Training Centre, 1066 Epalinges, Switzerland.

* Present address: Route de Berne 7A, 1700 Fribourg, Switzerland.

{dagger} To whom correspondence should be addressed. E-mail: nicolas.fasel{at}unil.ch

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