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Human hepatic stellate cells in primary culture are safe targets for Leishmania donovani

Published online by Cambridge University Press:  20 December 2012

O. ROSTAN ,
F. ROBERT-GANGNEUX ,
M. LAMBERT ,
M. SAMSON  and
J. P. GANGNEUX
O. ROSTAN
Affiliation:
INSERM U1085, IRSET, Université Rennes 1, 2 avenue du Professeur Léon Bernard, F-35043 Rennes, France
F. ROBERT-GANGNEUX
Affiliation:
INSERM U1085, IRSET, Université Rennes 1, 2 avenue du Professeur Léon Bernard, F-35043 Rennes, France Centre Hospitalier Universitaire de Rennes, Laboratoire de Parasitologie-Mycologie, 2 avenue du Professeur Léon Bernard, F-35033 Rennes, France
M. LAMBERT
Affiliation:
SFR Biosit UMS 3480 – U 018, Plateforme IBiSA MRic-Photonics, 2 avenue du Professeur Léon Bernard, F-35043 Rennes, France, 35043 Rennes Cedex, France
M. SAMSON
Affiliation:
INSERM U1085, IRSET, Université Rennes 1, 2 avenue du Professeur Léon Bernard, F-35043 Rennes, France
J. P. GANGNEUX*
Affiliation:
INSERM U1085, IRSET, Université Rennes 1, 2 avenue du Professeur Léon Bernard, F-35043 Rennes, France Centre Hospitalier Universitaire de Rennes, Laboratoire de Parasitologie-Mycologie, 2 avenue du Professeur Léon Bernard, F-35033 Rennes, France
*
*Corresponding author: Laboratoire de Parasitologie, Faculté de Médecine, 2 Avenue du Professeur Léon Bernard, 35043 Rennes, France. Tel.: 00332 23 23 44 90; Fax: 00332 23 23 46 29. E-mail address: jean-pierre.gangneux@univ-rennes1.fr
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Summary

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.

Keywords

Leishmania donovanivisceral leishmaniasisliverhepatic stellate cellssanctuary cellsasymptomatic carriagerelapses
Type
Research Article
Information
Parasitology , Volume 140 , Issue 4 , April 2013 , pp. 471 - 481
Copyright
Copyright © Cambridge University Press 2012

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