Chemotactic activities of vasoactive intestinal peptide, neuropeptide Y and substance P in Leishmania braziliensis

Cell-cell interaction and active migration (and invasion) of parasites into skin host-cell(s) are key steps for successful infection by Leishmania. Chemotaxis constitutes a primordial chapter of Leishmania-host cell interaction, potentially modulated by neuropeptides released into the skin due, for example, to the noxious stimuli represented by the insect bite. Herein we have evaluated in vitro the effect of sensory (Substance P, SP) and autonomic (Vasoactive Intestinal Peptide, VIP, and Neuropeptide Y, NPY) neuropeptides on parasite taxis, and investigated the potential modulatory effect of SP on Leishmania (Viannia) braziliensis-macrophage interaction. We demonstrated that VIP (10−10 M) and NPY (10−9 M) are chemorepellent to the parasites, while SP (10−8 M) produces a chemoattractant response. SP did not affect macrophage viability but seems to impair parasite-macrophage interaction as it decreased promastigote adherence to macrophages. As this effect is blocked by ([D-Pro 2, D-Trp7,9]-Substance P (10−6 M), the observed action may be mediated by neurokinin-1 (NK1) transmembrane receptors. VIP and NPY repellent chemotactic effect is impaired by their corresponding receptor antagonists. Additionally, they suggest that SP may be a key molecule to guide promastigote migration towards, and interaction, with dendritic cells and macrophage host cells. Putative receptor model associated with neuropeptide responses in Leishmania (V.) braziliensis promastigotes in vitro. Receptors and signaling molecules are included although still further confirmation is needed. [Display omitted] •Physiological VIP and NPY concentrations are chemorepellent to Leishmania parasites.•Physiological SP concentrations are chemoattractant to Leishmania parasites.•Physiological SP concentrations inhibit Leishmania parasites adherence to macrophages.•Neuropeptide effects are suppressed by their corresponding receptor antagonists.