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The C-type Lectin Receptors Dectin-1, MR, and SIGNR3 Contribute Both Positively and Negatively to the Macrophage Response to Leishmania infantum
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International audience. Macrophages act as the primary effector cells during Leishmania infection through production of reactive oxygen species (ROS) and interleukin-1β (IL-1β). 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-1β secretion. In contrast, SIGNR3 has divergent functions during Leishmania infantum pathogenesis; this CLR favored parasite resilience through inhibition of the LTB4-IL-1β 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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