Leishmania infantum Enhances Migration of Macrophages via a Phosphoinositide 3-Kinase γ-Dependent Pathway.

Leishmania infantum (L. infantum) and Leishmania major (L. major) are phylogenetically related protozoan parasites that cause different pathologies in humans (visceral and cutaneous infections, respectively). Here, we report on how these obligatory intracellular pathogens differentially affect the migration of macrophages. Resorting to gap closure assays of infected murine bone marrow derived macrophages, we observed that L. infantum enhances the mobility of these cells. This is not the case of L. major, whose impact on macrophage migration is null. Resorting to kinase inhibition assays, we witnessed that chemical inhibition of phosphoinositide 3-kinase-γ (PI3Kγ) critically impairs cell mobility in all experimental conditions. Importantly, the blockade of tyrosine kinases with dasatinib also slows down naı̈ve and L. major-parasitized cells but not macrophages exposed to L. infantum. The dasatinib-resistant phenotype of L. infantum-infected macrophages aligns with the hypothesis that this parasite invokes a tyrosine kinase-independent pathway to increase the PI3Kγ activity of macrophages and enhance migration.