The Immune Response to Sand Fly Salivary Proteins and Its Influence on Leishmania Immunity

Regis Gomes,Fabiano Oliveira

doi:10.3389/fimmu.2012.00110

Abstract

Leishmaniasis is a vector-borne disease transmitted by bites of phlebotomine sand flies. During Leishmania transmission, sand fly saliva is co-inoculated with parasites into the skin of the mammalian host. Sand fly saliva consists of roughly thirty different salivary proteins, many with known roles linked to blood feeding facilitation. Apart from the anti-hemostatic capacity of saliva, several sand fly salivary proteins have been shown to be immunogenic. Immunization with a single salivary protein or exposure to uninfected bites was shown to result in a protective immune response against leishmaniasis. Antibodies to saliva were not required for this protection. A strong body of evidence points to the role for saliva-specific T cells producing IFN-γ in the form of a delayed-type hypersensitivity reaction at the bite site as the main protective response. Herein, we review the immunity to sand fly salivary proteins in the context of its vector–parasite–host combinations and their vaccine potential, as well as some recent advances to shed light on the mechanism of how an immune response to sand fly saliva protects against leishmaniasis.

Highlights

Leishmaniasis is a vector-borne neglected disease caused by protozoan parasites of the genus Leishmania
The fact that sand fly salivary proteins are obligatorily inoculated with parasites within the skin of the vertebrate host is an important initial step that is still overlooked, because protective vaccines against Leishmania infective-challenge delivered by needle failed to control a vector-borne challenge (Peters et al, 2009) while multiple exposures to sand fly saliva induce an immune response that can control leishmaniasis in animal models (Belkaid et al, 1998)
Immune responses to the sand fly salivary proteins have been consistently shown in mice, hamsters, dogs, and humans following repeated exposure to bites or by injection of salivary glands dissected from female P. argentipes, P. ariasi, P. papatasi, P. sergenti, L. longipalpis, and L. intermedia (Ghosh and Mukhopadhyay, 1998; Belkaid et al, 2000; Kamhawi et al, 2000; Morris et al, 2001; Valenzuela et al, 2001; Silva et al, 2005; Thiakaki et al, 2005; Oliveira et al, 2006, 2008; de Moura et al, 2007; Jochim et al, 2008; Collin et al, 2009; Drahota et al, 2009; Ahmed et al, 2010; Ben Hadj Ahmed et al, 2010; Clements et al, 2010; Rohousova et al, 2011; Vlkova et al, 2011)

Summary

INTRODUCTION

Leishmaniasis is a vector-borne neglected disease caused by protozoan parasites of the genus Leishmania. The fact that sand fly salivary proteins are obligatorily inoculated with parasites within the skin of the vertebrate host is an important initial step that is still overlooked, because protective vaccines against Leishmania infective-challenge delivered by needle failed to control a vector-borne challenge (Peters et al, 2009) while multiple exposures to sand fly saliva induce an immune response that can control leishmaniasis in animal models (Belkaid et al, 1998). Maxadilan can act by inhibiting or modulating the inflammatory and immune response of mice, suggesting it contributes to the disease-exacerbating qualities of L. longipalpis saliva (Morris et al, 2001). It was recently shown that L. longipalpis saliva induced lipid body formation in murine macrophages in vitro and in vivo and these lipid bodies were linked www.frontiersin.org

Gomes and Oliveira

Bites Bites SGH SGH SGH SGH SGH SGH SGH SGH

Immune response

CONCLUSION