serval:BIB_A071D03EE498
Leishmaniavirus-Dependent Metastatic Leishmaniasis Is Prevented by Blocking IL-17A.
10.1371/journal.ppat.1005852
000385621900024
27658195
Hartley
M.A.
author
Bourreau
E.
author
Rossi
M.
author
Castiglioni
P.
author
Eren
R.O.
author
Prevel
F.
author
Couppié
P.
author
Hickerson
S.M.
author
Launois
P.
author
Beverley
S.M.
author
Ronet
C.
author
Fasel
N.
author
article
2016
PLoS Pathogens
1553-7374
1553-7366
journal
12
9
e1005852
Cutaneous leishmaniasis has various outcomes, ranging from self-healing reddened papules to extensive open ulcerations that metastasise to secondary sites and are often resistant to standard therapies. In the case of L. guyanensis (L.g), about 5-10% of all infections result in metastatic complications. We recently showed that a cytoplasmic virus within L.g parasites (LRV1) is able to act as a potent innate immunogen, worsening disease outcome in a murine model. In this study, we investigated the immunophenotype of human patients infected by L.g and found a significant association between the inflammatory cytokine IL-17A, the presence of LRV1 and disease chronicity. Further, IL-17A was inversely correlated to the protective cytokine IFN-γ. These findings were experimentally corroborated in our murine model, where IL-17A produced in LRV1+ L.g infection contributed to parasite virulence and dissemination in the absence of IFN-γ. Additionally, IL-17A inhibition in mice using digoxin or SR1001, showed therapeutic promise in limiting parasite virulence. Thus, this murine model of LRV1-dependent infectious metastasis validated markers of disease chronicity in humans and elucidated the immunologic mechanism for the dissemination of Leishmania parasites to secondary sites. Moreover, it confirms the prognostic value of LRV1 and IL-17A detection to prevent metastatic leishmaniasis in human patients.
eng
60_published
true
peer-reviewed
University of Lausanne
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