title: Human hepatic stellate cells in primary culture are safe targets for Leishmania donovani.
abstract: Leishmania parasites can escape the immune response by invading cell types lacking leishmanicidal mechanisms. Silent persistence of Leishmania parasites in the host organism is responsible for asymptomatic carriage and relapses after cured leishmaniasis. Here, we studied the interaction between Hepatic Stellate Cells (HSC) and Leishmania. An original model of human HSC in primary culture infected with L. donovani was developed. The presence of intracellular parasites was studied and quantified using optical and confocal microscopy. HSC characteristics were studied using microscopy, methylene blue assay, long-term cultures and qPCR. We showed for the first time that human HSC are permissive to L. donovani infection, with no modification of HSC survival, growth rate and proinflammatory and fibrogenic characteristics. Intracellular parasites did not replicate but HSC had no effect on their survival. Indeed, after a 40-day culture, infected HSC cultures transferred on NNN medium yielded new promastigotes that were able to proliferate and efficiently infect new cells. HSC are permissive to L. donovani, with neither parasite killing nor apparent cell damage. Thus, HSC could act as potent sanctuary cells for Leishmania in the liver, which could partially explain parasite reactivation after an asymptomatic carriage or a cured visceral leishmaniasis.
authors.affiliation: INSERM U1085, IRSET, Université Rennes 1, 2 avenue du Professeur Léon Bernard, F-35043 Rennes, France.
authors.forename: O
authors.initials: O
authors.lastname: Rostan
authors.forename: F
authors.initials: F
authors.lastname: Robert-Gangneux
authors.forename: M
authors.initials: M
authors.lastname: Lambert
authors.forename: M
authors.initials: M
authors.lastname: Samson
authors.forename: J P
authors.initials: JP
authors.lastname: Gangneux
mesh_terms: D002478:Cells, Cultured; D020869:Gene Expression Profiling; D055166:Hepatic Stellate Cells / Q000469:parasitology*; D006801:Humans; D007893:Leishmania donovani / Q000502:physiology*; D007898:Leishmaniasis, Visceral