Saliva Drives Interleukin-17-Induced Neutrophil Recruitment Favoring Infection

During bloodfeeding, the presence of sand fly saliva in the hemorrhagic pool where is also inoculated modulates the development of host immune mechanisms creating a favorable environment for disease progression. To date, information obtained through experimental models suggests that sand fly saliva induces cellular recruitment and modulates production of eicosanoids. However, the effect of sand fly saliva in the different steps of the inflammatory response triggered by remains undefined. Here we further investigate if interaction of salivary gland sonicate (SGS) with different host cells present during the initial inflammatory events regulate infectivity. Initially, we observed that incubation of human peripheral blood mononuclear cells (PBMC) with SGS in the presence of significantly increased IL-10 but did not alter expression of IFN-γ and TNF-α by CD4 T cells induced by the parasite alone. Interestingly, incubation of PBMC with SGS alone or in the presence of resulted in increased IL-17 production. The presence of IL-17 is related to neutrophil recruitment and plays an important role at the site of infection. Here, we also observed increased migration of neutrophil using an chemotactic assay following incubation with supernatants from PBMC stimulated with and SGS. Neutrophil migration was abrogated following neutralization of IL-17 with specific antibodies. Moreover, culture of human neutrophils with in the presence of SGS promoted neutrophil apoptosis resulting in increased parasite viability. Neutrophils operate as the first line of defense in the early stages of infection and later interact with different cells, such as macrophages. The crosstalk between neutrophils and macrophages is critical to determine the type of specific immune response that will develop. Here, we observed that co-culture of human macrophages with autologous neutrophils previously infected in the presence of SGS resulted in a higher infection rate, accompanied by increased production of TGF-β and PGE. Our results provide new insight into the contribution of SGS to -induced regulation of important inflammatory events, creating a favorable environment for parasite survival inside different host cells.