Abstract

During bloodfeeding, the presence of sand fly saliva in the hemorrhagic pool where Leishmania 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 Leishmania remains undefined. Here we further investigate if interaction of Lutzomyia longipalpis salivary gland sonicate (SGS) with different host cells present during the initial inflammatory events regulate Leishmania infantum infectivity. Initially, we observed that incubation of human peripheral blood mononuclear cells (PBMC) with Lu. longipalpis SGS in the presence of L. infantum 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 Lu. longipalpis SGS alone or in the presence of L. infantum 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 in vitro chemotactic assay following incubation with supernatants from PBMC stimulated with L. infantum and Lu. longipalpis SGS. Neutrophil migration was abrogated following neutralization of IL-17 with specific antibodies. Moreover, culture of human neutrophils with L. infantum in the presence of Lu. longipalpis 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 Lu. longipalpis SGS resulted in a higher infection rate, accompanied by increased production of TGF-β and PGE2. Our results provide new insight into the contribution of Lu. longipalpis SGS to L. infantum-induced regulation of important inflammatory events, creating a favorable environment for parasite survival inside different host cells.

Highlights

  • Leishmania transmission occurs through the bite of infected female sand flies

  • We investigated if stimulation with L. infantum in the presence of Lu. longipalpis sonicate from Lu. longipalpis (SGS) was able to modulate expression of cytokines by T cells obtained from healthy volunteers

  • The present study provides further evidence that Lu. longipalpis saliva plays an important role on the different steps of the inflammatory response initiated after transmission

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Summary

Introduction

Leishmania transmission occurs through the bite of infected female sand flies. Bloodfeeding causes tissue damage creating a hemorrhagic pool resulting from probing and destruction of small capillaries. Neutrophils are the first cells to rapidly mobilize and quickly internalize parasites at the site of infection (Peters et al, 2009) They modify the course of immunity and infection with different Leishmania species (McFarlane et al, 2008; Peters et al, 2009; Ritter et al, 2009; Charmoy et al, 2010; Ribeiro-Gomes et al, 2012; Sousa et al, 2014) and are able to promote activation and recruitment of different leukocytes (Ribeiro-Gomes et al, 2012; Schuster et al, 2013; Sousa et al, 2014). IL-17 induces iNOS activation, expression of granulocyte macrophage colony stimulating factor and several cytokines and chemokines This results in the recruitment of leukocytes, especially neutrophils, creating a robust inflammatory infiltrate (Kolls and Linde, 2004). The possible role of sand fly saliva on IL-17 production during Leishmania infection remains unclear

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