title: Leishmania RNA virus controls the severity of mucocutaneous leishmaniasis.
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.
authors.affiliation: Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland.
authors.forename: Annette
authors.initials: A
authors.lastname: Ives
authors.forename: Catherine
authors.initials: C
authors.lastname: Ronet
authors.forename: Florence
authors.initials: F
authors.lastname: Prevel
authors.forename: Giulia
authors.initials: G
authors.lastname: Ruzzante
authors.forename: Silvia
authors.initials: S
authors.lastname: Fuertes-Marraco
authors.forename: Frederic
authors.initials: F
authors.lastname: Schutz
authors.forename: Haroun
authors.initials: H
authors.lastname: Zangger
authors.forename: Melanie
authors.initials: M
authors.lastname: Revaz-Breton
authors.forename: Lon-Fye
authors.initials: LF
authors.lastname: Lye
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Hickerson
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Beverley
authors.forename: Hans
authors.initials: H
authors.lastname: Acha-Orbea
authors.forename: Pascal
authors.initials: P
authors.lastname: Launois
authors.forename: Nicolas
authors.initials: N
authors.lastname: Fasel
authors.forename: Slavica
authors.initials: S
authors.lastname: Masina
mesh_terms: D000818:Animals; D018925:Chemokines / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D018334:Leishmania guyanensis / Q000472:pathogenicity* / Q000821:virology*; D007897:Leishmaniasis, Mucocutaneous / Q000276:immunology* / Q000469:parasitology; D019199:Leishmaniavirus / Q000276:immunology* / Q000502:physiology; D008264:Macrophages / Q000276:immunology / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018512:Parasitemia; D010588:Phagosomes / Q000469:parasitology; D012330:RNA, Double-Stranded / Q000276:immunology; D012367:RNA, Viral / Q000276:immunology; D051196:Toll-Like Receptor 3 / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology
chemical_list: D018925:Chemokines; D016207:Cytokines; D018836:Inflammation Mediators; D012330:RNA, Double-Stranded; D012367:RNA, Viral; D051196:Toll-Like Receptor 3; D051193:Toll-Like Receptors