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Exosome Release by Leismania Parasite in Vector Sand Fly’s Gut Is Key to Protozoan's Infectious Life Cycle; Exosomes & Leismania Parasites Are Both Transmitted When Fly Takes Blood Meal; Exosomes Enhance Parasite Pathogenicity

A team of international scientists led by Dr. Martin Olivier from the Research Institute of the McGill University Health Centre (RI-MUHC) has discovered an important mechanism underlying the pathogenicity of leishmaniasis, a deadly parasitic disease caused by protozoans of the Leishmania genus that are transmitted by to humans by sandfly bites. The disease affects over 12 million people worldwide, and more than 1.3 million new cases are reported every year. In the new study, published online on October 22, 2015 in an open-access article in Cell Reports, the researchers describe how sub-cellular vesicles known as exosomes, boost the process by which the Leishmania parasite infects humans and other mammals. These findings could lead to the development of new potential vaccine targets and diagnostic tools for leishmaniasis and other parasitic diseases. The article is titled “Exosome Secretion by the Parasitic Protozoan Leishmania within the Sand Fly Midgut.” “Our study reports the first observation that a pathogen within its insect vector can release extracellular vesicles or exosomes that are an integral part of the parasite's infectious life cycle,'' states the study's lead author Dr. Olivier, a researcher from the Infectious Diseases and Immunity in Global Health Program of the RI-MUHC and a full Professor of Medicine at McGill University. "This means that any bacteria and parasites transmitted via insect blood meals could use a similar strategy to extend their successful infection.'' Exosomes are small, cell-derived vesicles that are present in all biological fluids, including blood, urine, saliva, etc. Exosomes have been the focus of numerous studies, particularly due to their apparent involvement in communication between cells, especially immune and tumor cells. Despite the abundant knowledge obtained through studies using exosomes within in vitro experiments, Dr. Olivier's team, with colleagues from the National Institutes of Health, is believed to be the first to describe, step-by-step, the formation and release of exosomes in a living organism in relation to a specific infectious agent.

"By using electron microscopy and proteomic analysis, we discovered that the parasite was releasing exosomes within the gut of the female sandflies,'' explains the study's first author Dr. Vanessa Diniz Atayde, who is a research associate in Dr. Olivier's laboratory. "As the insect took a blood meal from its host, both exosomes and Leishmania were transmitted.''

"We also found that by injecting the parasite with its exosomes in mice models, we were enhancing the pathogenicity of the parasite," adds Dr. Olivier. "The inflammatory response, usually caused by an infection, and the number of parasites were increased.''

Leishmaniasis is found in parts of the tropics, subtropics, and southern Europe, and is transmitted through the bite of female phlebotomine sandflies. The parasites are injected through the skin and are ingested by macrophages, where they block immune function and multiply, forming skin lesions and spreading to other tissues in the body depending on the Leishmania species involved.

This infectious disease can occur in cutaneous forms, which are generally curable, as well as in a more dangerous - and potentially fatal - visceral form. The World Health Organization estimates that 20,000 to 30,000 deaths are caused annually by Leishmania worldwide.

In North America, leishmaniasis is indigenous to México and Texas, but has begun to expand its range northward. Further expansion to the north may be facilitated by climate change as more habitat becomes suitable for insect vectors and reservoir species for the disease.

"These findings could open the door to the development of new vaccines targeting the exosome components by neutralizing its ability to boost infection, ''says Dr. Olivier.

"Another interesting aspect of this study is that by studying the exosomes of other biting insects that suck blood, such as mosquitoes or black flies, we could develop anti-allergic therapy to tone-down developed skin inflammation in certain persons upon an insect bite."

The authors conclude that “Our data indicate that Leishmania exosomes are an integral part of the parasite’s infectious life cycle, and we propose to add these vesicles to the repertoire of virulence factors associated with vector-transmitted infections.”

The images show small exosomes (indicated by the red arrows) being released by the Leishmaniasis parasite.(Credit: Dr. Martin Olivier, Research Institute of the McGill University Health Centre). Please see the press release (at link below) to view higher-resolution images of these exosomes.

[Press release] [Cell Reports article]

[The Scientist article] [ article] [Infection Control Today article]