Leishmania RNA virus controls the severity of mucocutaneous leishmaniasis

Annette Ives, Catherine Ronet, Florence Prevel, Giulia Ruzzante, Silvia Fuertes-Marraco, Frederic Schutz, Haroun Zangger, Melanie Revaz-Breton, Lon Fye Lye, Suzanne M. Hickerson, Stephen M. Beverley, Hans Acha-Orbea, Pascal Launois, Nicolas Fasel, Slavica Masina

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199 Scopus citations

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.

Original languageEnglish
Pages (from-to)775-778
Number of pages4
JournalScience
Volume331
Issue number6018
DOIs
StatePublished - Feb 11 2011

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    Ives, A., Ronet, C., Prevel, F., Ruzzante, G., Fuertes-Marraco, S., Schutz, F., Zangger, H., Revaz-Breton, M., Lye, L. F., Hickerson, S. M., Beverley, S. M., Acha-Orbea, H., Launois, P., Fasel, N., & Masina, S. (2011). Leishmania RNA virus controls the severity of mucocutaneous leishmaniasis. Science, 331(6018), 775-778. https://doi.org/10.1126/science.1199326