AUTHOR=Gomes Regis , Oliveira Fabiano TITLE=The Immune Response to Sand Fly Salivary Proteins and Its Influence on Leishmania Immunity JOURNAL=Frontiers in Immunology VOLUME=Volume 3 - 2012 YEAR=2012 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2012.00110 DOI=10.3389/fimmu.2012.00110 ISSN=1664-3224 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 upon multiple contacts with a mammalian host. Immunization with single immunogenic salivary proteins or exposure to uninfected bites can produce protective immune responses against leishmaniasis. These sand fly salivary proteins induce cellular immune responses and/or antibodies. Antibodies to saliva are not required for protection in a mouse model against leishmaniasis. 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 immunity to sand fly salivary proteins in the context of its vector-parasite-host combinations and 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.