Influência da saliva do vetor Nyssomyia whitmani (Diptera: Psychodidae) em macrófagos M0, M1 e M2 infectados por Leishmania (Leishmania) amazonensis (Kinetoplastida: Trypanosomatidae)

Abstract

Leishmaniasis are neglected diseases transmitted to animals and humans by the bite of an infected female sand fly. Leishmania parasites (Kinetoplastida: Trypanosomatidae) are the causative agents of leishmaniasis inoculated with sandfly salivainto the host

skin. Saliva contains pharmacologically active compounds with antihemostatic, anti- inflammatory and immunomodulatory properties. In mammals, the chemotactic

response elicits an intense inflammatory cell infiltrate containing mainly neutrophils, eosinophils, and macrophages. Macrophages are leukocytic cells specialized in tissue remodeling and in the immune response to pathogens, like Leishmania parasites. These cells may respond to infection in a resistant manner, destroying the internalized parasites or providing an ideal microenvironment for pathogen proliferation, relying on the macrophage phenotypes. Some mechanisms of the immunological response of macrophages may be prevented by the insect vector saliva, such as the inhibition of NO production by the decrease of iNOS expression and the antigen presentation by macrophages to T CD4+

lymphocytes since it inhibits the antigen-presenting capacity of macrophages through class II MHC pathway. Based on the premise that vector saliva modulates the macrophage immune response, the goal of this study was to evaluate the macrophage immune response, polarized or not, stimulated with Nyssomyia whitmani saliva during Leishmania amazonensis infection. It was observed that vector saliva induces intense proliferation of promastigotes during the first 24 hours after contact, which can lead to a rapid expansion of the parasite. The earlier contact between macrophage and saliva increases the parasite burden differently from what occurs in the following exposure to infection, and the cytokine production, which leads to macrophage modulation, and metabolite production, e.g., hydrogen peroxide and NO, both known as leishmanicidal agents. As for the polarized macrophages, saliva inhibits NO production in M1 macrophages and affects the expression of some surface receptors and intracellular enzymes, showing a modulation to an anti-inflammatory phenotype, even in preactivated macrophages. Saliva also induces an increase in stimulated macrophage viability, even in the presence of Leishmania. The increase in cell survival can enable leishmaniasis development and the extension of the internalized parasite expansion. From the presents results, it can be seen the great relevance of vectors in the establishment of Leishmania in macrophages.