%0 Journal Article
%9 ACL : Articles dans des revues avec comité de lecture répertoriées par l'AERES
%A Lefevre, L.
%A Lugo-Villarino, G.
%A Meunier, E.
%A Valentin, A.
%A Olagnier, D.
%A Authier, H.
%A Duval, C.
%A Dardenne, C.
%A Bernad, J.
%A Lemesre, Jean-Loup
%A Auwerx, J.
%A Neyrolles, O.
%A Pipy, B.
%A Coste, A.
%T The C-type lectin receptors dectin-1, MR, and SIGNR3 contribute both positively and negatively to the macrophage response to Leishmania infantum
%D 2013
%L PAR00011482
%G ENG
%J Immunity
%@ 1074-7613
%M ISI:000330942500020
%N 5
%P 1038-1049
%R 10.1016/j.immuni.2013.04.010
%U https://www.documentation.ird.fr/hor/PAR00011482
%V 38
%W Horizon (IRD)
%X Macrophages act as the primary effector cells during Leishmania infection through production of reactive oxygen species (ROS) and interleukin-1 beta (IL-1 beta). However, how macrophage-killing mechanisms are activated during Leishmania-macrophage interactions is poorly understood. Here, we report that the macrophage response against Leishmania infantum in vivo is characterized by an M2b-like phenotype and C-type lectin receptors (CLRs) signature composed of Dectin-1, mannose receptor (MR), and the DC-SIGN homolog SIGNR3 expression. Dectin-1 and MR were crucial for the microbicidal response as indicated by the fact that they activated Syk-p47phox and arachidonic acid (AA)-NADPH oxidase signaling pathways, respectively, needed for ROS production and also triggered Syk-coupled signaling for caspase-1-induced IL-1 beta secretion. In contrast, SIGNR3 has divergent functions during Leishmania infantum pathogenesis; this CLR favored parasite resilience through inhibition of the LTB4-IL-1 beta axis. These pathways also operated during infection of primary human macrophages. Therefore, our study promotes CLRs as potential targets for treatment, diagnosis, and prevention of visceral leishmaniasis.
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