Leishmania infantum parasites Aurélie Schwing 1 2 3 Didier F Pisani 4 Christelle Pomares 12 Alissa Majoor 2 Sandra LacasGervais 5 Emmanuel Lemichez 6 Pierre Marty ID: 935570
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Slide1
Identification of adipocytes as target cells forLeishmania infantum parasites
Aurélie Schwing1, 2, 3, Didier F Pisani4, Christelle Pomares1,2,*, Alissa Majoor2, Sandra Lacas-Gervais5, Emmanuel Lemichez6, Pierre Marty1,2, Laurent Boyer2, Grégory Michel21Université Côte d’Azur, Centre Hospitalier Universitaire l’Archet, Parasitologie-Mycologie – Nice (France), 2Université Côte d’Azur, Inserm, U1065, C3M - Nice (France), 3Université Aix-Marseille- Marseille (France), 4Université Côte d’Azur, CNRS, Inserm, LP2N - Nice (France), 5Université Côte d’Azur, Centre Commun de Microscopie Appliquée - Nice (France), 6Institut Pasteur, Unité des toxines bactériennes - Paris (France), *pomares.c@chu-nice.fr
Slide2INTRODUCTION Leishmania infantum is responsible of visceral leishmaniasis (VL) transmitted by the bite of female sand fliesAccording to the WHO, 1 billion people at risk in endemic areas50 000 to 90 000 new cases per year worldwide90 – 97% survival chance when timely treatment
In humans, there are more asymptomatic carriers than people developing VLThat lead to the question about the safe targets of L. infantum
Slide3INTRODUCTION Adipose tissue has been proposed as a sanctuary of persistence for several pathogensWe investigated whether L. infantum could be found in adipose tissue
Slide4METHODSL. infantum GFP
LeIn vitro and in vivo experiments were performed with Recombinant L. infantum - expressing the Green Fluorescence ProteinMouse adipocytes were infected, and PCR, confocal and electron microscopy were used to follow the infectionGFP-L. infantum
Brown fat cell
Brite
fat cell
White fat cell
Slide5RESULTS1. L. infantum is found in the adipose tissue of infected mice
6 weeks p.i., Brown and White adipose tissue present parasite burdenwhich remained high in Brown adipose tissue 10 weeks p.i.
Slide6RESULTS1. L. infantum is found in the adipose tissue of infected mice
L. infantum persist in Brown adipose tissue after infection by the intravenous route
Slide7RESULTS2. L. infantum is present in adipocyte-enriched fractions
SVF: stromal vascular fractionPerilipin 1: a protein coating the lipid droplet, expressed only in white and brown adipocytesAdiponectin: a glycoprotein adipocyte-specific factor 18, specifically detected in the adipocyte fractionmRNA expression of
Slide8DNA parasite was detected adipocytes enriched fraction
RESULTS2. L. infantum is present in adipocyte-enriched fractions
Slide9RESULTS
2. L. infantum is present in adipocyte-enriched fractions No parasite DNA was detected in the stromal vascular fraction of each kind of adipose tissue
Slide10RESULTS
2. L. infantum is present in adipocyte-enriched fractions These results confirmed the in vivo localization of L. infantum in adipocytes
Slide11RESULTS3. L. infantum
can infect in vitro murine adipocytesprimary mouse pre-adipocytes brown, brite and white adipocytes 24, 48 and 72 hours post-infection presence of intracellular parasites into adipose tissueL. infantum can infect:brown, brite and white adipocytesBrite adipocyte are similar to classical brown adipocytes although they are derived from white adipose tissue
Slide12RESULTS
4. L. infantum parasites were found inside non lipid droplet adipocyte vacuole We performed an electron microscopy experiment.L. infantum parasites were indeed found inside a vacuole within lipid droplet-containing cells. By combining epifluorescence and electron microscopy approaches, we confirmed the ability of L. infantum to parasitize adipocytes
Slide13CONCLUSIONAll together our
results suggest adipocytes as a ‘safe target’ for L. infantum parasitesTreatment with poor access to the adipose tissue would be poorly effective at resolving the infection Probably have an impact on relapses with parasite exiting the adipocytes
In this context, it would
be interesting to define new drugs against
L. infantum with penetration
into
adipocytes to
efficiently
target
parasites
within
these
cells
Slide14THANK YOU FOR YOUR ATTENTIONAurélie Schwing Didier F PisaniAlissa
MajoorSandra Lacas-GervaisEmmanuel LemichezLaurent BoyerPierre MartyGrégory MichelUniversité Côte d’Azur,Centre Hospitalier Universitaire l’Archet, Parasitologie-Mycologie – Nice Université Aix-Marseille- Marseille Centre Commun de Microscopie Appliquée NiceInstitut Pasteur, Unité des toxines bactériennes Paris