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A. Ives et al., “Leishmania RNA virus controls the severity of mucocutaneous leishmaniasis,” Science, 331:775-78, 2011. Free F1000 Evaluation
The parasite Leishmania—which forms large, slow-healing sores when it attacks the skin (cutaneous leishmaniasis, CL)—can become more aggressive, metastasizing to the nasal passages and throat, a condition called mucocutaneous leishmaniasis, or MCL. Researchers knew that several Leishmania species harbor a double-stranded RNA virus called LRV1, but they didn’t know if it contributed to MCL. Nicolas Fasel from the University of Lausanne, Switzerland, and colleagues showed that the MCL parasite is more heavily infected with the virus, and that the resulting pathology is caused by overstimulation of the host immune system.
The researchers isolated metastatic strains of Leishmania and noticed that they induced sustained production of chemokines and cytokines in macrophages in vitro. But blocking phagocytosis prevented the hyperinflammatory response associated with MCL.
The researchers hypothesize that when the parasites were lysed within the cells, they released their viral hitchhikers. The virus’s double-stranded RNA would bind to intracellular Toll-like receptors, triggering inflammatory pathways. Indeed, when the team tested macrophages functionally deficient in Toll-like receptors, the reaction was hampered.
If doctors could parse patients into MCL and CL groups, using the level of virus in their parasites as a marker, they could avoid unnecessary treatment of the 90 percent of infected patients whose CL clears on its own, said Phillip Scott, professor of immunology at the University of Pennsylvania, who was not involved with the research.