Molecular cell biology of Leishmania
I have a longstanding interest in the biology of protozoan parasites called trypanosomatids, which cause diseases in humans and animals in many of the poorest countries in the world.
Leishmania are transmitted by the bite of the sand fly and cause a spectrum of diseases, with symptoms ranging from mild but potentially disfiguring cutaneous lesions to life threatening visceral infections. A population of 350 million people globally are at risk of leishmaniasis, and the WHO estimates that 12 million people are currently infected. In the human body, Leishmania parasites are taken up by macrophages and proliferate within the harsh conditions of the phagolysosome.
Much remains unclear about the molecular and cellular mechanisms that enable Leishmania to subvert macrophage defense mechanisms and cause disease.
The role of the flagellum in host-parasite interactions
Cilia and flagella are cellular projections built around a microtubule axoneme whose molecular architecture is highly conserved across eukaryotic groups. Cilia and flagella serve two main functions: motility and sensory perception. Many cell types (ranging from single celled organisms such as Leishmania to mammalian sperm cells) use their motile flagellum for locomotion. Sensory cilia serve a wide range of functions. In the human body, cilia are important for the detection of developmental signals, and the perception of chemical and mechanical stimuli. Comparative genomic studies have suggested that the last common ancestor of eukaryotes had a flagellum that was both motile and sensory. What sensory functions, if any, are conserved in the Leishmania flagellum remains unknown.
We have recently discovered that the flagellum of the intracellular Leishmania parasite structurally resembles sensory cilia and put forward the hypothesis that the parasite flagellum could act as a ‘cellular antenna’ with functions in host-parasite interactions. We also found that the tip of the amastigote flagellum associates closely with the membrane of the host cell vacuole. The flagellar membrane forms a distinct surface, and we are now studying the molecular composition of this domain to discover what receptors or transporters are expressed in the amastigote form and how they contribute to the parasite’s ability to sense its environment and survive in the macrophage.
Gluenz et al., (2010) FASEBJ 24, 3117-21