Infection & Immunity

The Leishmania Laboratory - Leishmaniasis

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Leishmaniasis

Leishmaniasis is caused by a protozoan parasite with a predilection for a specific host cell, the macrophage. The flagellated form of the parasite, the promastigote is introduced into the human host by the blood sucking sandfly, Phlebotomus. Promastigotes attach to mononuclear phagocytes via a receptor-mediated mechanism, are taken up by phagocytosis into a phagosome which fuses to lysosomes to form the phagolysosome. Once inside the macrophage, the promastigotes undergo significant biochemical and metabolic changes, which result in the obligatory intracellular form of the parasite, the amastigote. In addition to macrophages, dendritic cells and fibroblasts may also harbour the organism. However, Leishmania have evolved mechanisms to subvert these host “seek and destroy” cells for their survival.

Movie of invasion by promastigotes and amastigotes

Leishmaniasis is a spectrum of diseases of different clinical manifestations depending on a combination of host and parasite genetic factors. Thus, Leishmania donovani tends to home to the liver and spleen causing (usually fatal) visceral leishmaniasis, Leishmania brasiliensis homes to the lining of the nose and throat causing the mutilating mucocutaneous disease, and Leishmania major homes to the skin causing the self limiting skin ulcers, called cutaneous leishmaniasis.

Leishmaniasis affects at least 12 million individuals each year, with about 300 million people at risk, both in the developed and developing world. In the last decade, visceral leishmaniasis has surged in epidemic proportions in new areas in the Sudan, in Pakistan and in China. It has also become a major problem in AIDS patients in Europe and South America.

To date, there is no vaccine against leishmaniasis, and the drugs available are toxic, expensive, and difficult to adminster. Moreover, there is evidence of emerging resistance of the parasites to the commonly used antimony drugs.

The major aim of our group is to use state of the art biochemical and molecular tools in order to understand the biology of the parasite and its interaction with the host. We believe that this is the only way which will allow the identification of parasite targets for design of vaccines and new and specific drugs.

The group has focused on the skin disease caused by Leishmania major because of strong evidence that host-protective immunity develops naturally in individuals who recover from the disease. Moreover, we reasoned that the availability of an excellent mouse model for disease may allow us to ask questions about the host-parasite interaction which are directly relevant to the human disease.

What follows is a brief description of the issues that we are investigating and how they fit into the overall picture of this host-parasite system. The approaches that we take range from genetics and immunology through to cell and molecular biology.

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