TY - JOUR
T1 - Leishmania RNA virus controls the severity of mucocutaneous leishmaniasis
AU - Ives, Annette
AU - Ronet, Catherine
AU - Prevel, Florence
AU - Ruzzante, Giulia
AU - Fuertes-Marraco, Silvia
AU - Schutz, Frederic
AU - Zangger, Haroun
AU - Revaz-Breton, Melanie
AU - Lye, Lon Fye
AU - Hickerson, Suzanne M.
AU - Beverley, Stephen M.
AU - Acha-Orbea, Hans
AU - Launois, Pascal
AU - Fasel, Nicolas
AU - Masina, Slavica
PY - 2011/2/11
Y1 - 2011/2/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79951488203&partnerID=8YFLogxK
U2 - 10.1126/science.1199326
DO - 10.1126/science.1199326
M3 - Article
C2 - 21311023
AN - SCOPUS:79951488203
SN - 0036-8075
VL - 331
SP - 775
EP - 778
JO - Science
JF - Science
IS - 6018
ER -