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Role of invariant NKT lymphocytes in the hepatic granulomatous response to Leishmania donovani infection

Abstract number: P962

Drogoul A.S., Robert-Gangneux F., Lisbonne M., Turlin B., Guiguen C., Herbelin A., Samson M., Gangneux J.P.

Objectives: Visceral leishmaniasis (VL) is a life-threatening infection due to protozoan parasites from the Leishmania genus. L. donovani in India and East Africa, and L. infantum in the mediterranean basin as well as in Brazil are the responsible species for VL. During VL, the hepatic granulomatous response is correlated to the parasitic clearance. However, cellular organisation of mature granulomas is still not totally understood, but seems to involve NKT cells. This particular cell population, at the interface of innate and acquired immunity harbours surface molecules from both NK and T (TCRab) cells. Among NKT cells, invariant NKT lymphocytes (iNKT) are hepatic parenchymatous cells that harbours a semi-invariant TCR, Valpha14-Jalpha18, associated to restricted beta chains. Here, we analyse their role in the granulomatous response during liver infection with L. donovani in a murine model deleted in iNKT cells.

Methods: C57BL/6 Ja18-/- mice and congenic wild-type mice were infected with L. donovani promastigotes. At days 15, 30 and 60, groups of 4 mice were sacrificed in order to analyse:

–the hepatic parasitic load on May Grunwald-Giemsa stained smears,

–the hepatic granulomatous response on hemalun-eosin-safran stained histological sections,

–the hepatic damage that was evaluated by dosing alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactico-dehydrogenase and alcaline phosphatase levels in the serum.

Results: Compared to wild-type mice that rapidly control the infection, iNKT-/- mice presented with significantly higher hepatic parasitic loads until 10-fold more, at D15 and D30. In parallel, the histologic examination of liver sections displayed a delay in the granuloma maturation. iNKT-/- mice presented at D30 with few large granulomas (13.3% with > 25 cells) versus 33.6% in wild-types, and granuloma maturation was reached in 20% of them versus 50%, respectively. At D60, 40% of the granulomas were matures in iNKT-/- mice and the parasitic loads declined until similar results to wild-types. Hepatic enzyme dosages showed a similar hepatocyte damage in both groups without statistically significant difference.

Conclusion: Finally, our data underline the role of iNKT lymphocytes in the early and efficient organisation of hepatic granuloma that warrants a clearance of parasites. In C57/Bl6 mice that exhibit a resistant phenotype to Leishmania infection, the settlement of the adaptative response allows a definitive cure of the infection.

Session Details

Date: 19/04/2008
Time: 00:00-00:00
Session name: 18th European Congress of Clinical Microbiology and Infectious Diseases
Subject:
Location: Barcelona, Spain
Presentation type:
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