Journal article
Type I interferons induced by endogenous or exogenous viral infections promote metastasis and relapse of leishmaniasis
M Rossi, P Castiglioni, MA Hartley, RO Eren, F Prével, C Desponds, DT Utzschneider, D Zehn, MG Cusi, FM Kuhlmann, SM Beverley, C Ronet, N Fasel
Proceedings of the National Academy of Sciences of the United States of America | NATL ACAD SCIENCES | Published : 2017
Abstract
The presence of the endogenous Leishmania RNA virus 1 (LRV1) replicating stably within some parasite species has been associated with the development of more severe forms of leishmaniasis and relapses after drug treatment in humans. Here, we show that the disease-exacerbatory role of LRV1 relies on type I IFN (type I IFNs) production by macrophages and signaling in vivo. Moreover, infecting mice with the LRV1-cured Leishmania guyanensis (LgyLRV1.) strain of parasites followed by type I IFN treatment increased lesion size and parasite burden, quantitatively reproducing the LRV1-bearing (LgyLRV1+) infection phenotype. This finding suggested the possibility that exogenous viral infections could..
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Awarded by National Institutes of Health
Funding Acknowledgements
We thank S. Masina for critical reading of the manuscript and J. Boon for comments on an early draft of the manuscript. This work was funded by the Swiss National Fund for Research (Grants 310030153204 and IZRJZ3_164176), the Institute for Arthritis Research, the Pierre Mercier Foundation, and the NIH (Grants R56AI099364 and R01AI029646).