Leishmaniasis parasites 'persuade immune cells to invite them to dinner'
26 August 2009
The leishmaniasis disease is transmitted by sand flies. Dr Matthew Rogers, a Wellcome Trust Advanced Training Fellow at Imperial College London, and colleagues found that a gel produced by the Leishmania parasites entices immune cells called macrophages to the site of the sand fly bite. Macrophages normally kill invading bodies by ingesting and digesting them. However, the gel persuades the macrophages to instead engulf the parasite and provide nutrients.
The scientists say the findings will improve our understanding of the way the parasites establish infection and could aid the search for a leishmaniasis vaccine.
Leishmaniasis affects around 12 million people worldwide each year, mainly in tropical and sub-tropical countries. Symptoms include disfigurement and painful skin ulcers, which can lead to social exclusion. There is currently no vaccine for the disease.
Sand flies carry the Leishmania parasites in their gut. The parasite produces a gel - promastigote secretory gel (PSG) - that acts as a plug in the fly's gut, forcing it to expel the plug before it can feed on humans. Until now, it was thought that this was the gel's main function, with previous research suggesting it was the fly's saliva that helped the Leishmania parasite establish infection.
But in the new study conducted in mice, the researchers found that PSG attracted five times more macrophages to the bite site than sand fly saliva.
They found that PSG influences the macrophages to produce nutrients for the parasites. This happens within the first few days following infection, enabling the parasites to establish themselves.
The team's laboratory studies also showed that PSG helps more parasites survive the first 48 hours following infection - both the proportion of infected cells and the number of parasites in the cells increased up to eight times when PSG was present.
"Leishmania parasites are very cunning - they make their own gel to control the human immune system so they can establish a skin infection," said Dr Rogers, who led the research.
"Our previous work in mice has suggested that injecting a synthetic version of the gel into people might provide them with some protection against infection and we would like to explore this further."
Image: A female phlebotomine sand fly feeding on the tail of a mouse. Credit: Swiss Tropical Institute, Wellcome Images
Reference
Rogers M et al. Proteophosophoglycans regurgitated by Leishmania-infected sand flies target the L-arginine metabolism of host macrophages to promote parasite survival. PLoS Pathog 2009: 5(8) e1000555.