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

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.

Sand fly saliva: toward a vaccine against leishmaniases

“…In CL cases, anti-saliva antibodies have been shown to induce inflammation and vasculitis resulting in a greater numbers of harboring cells, especially the local neutrophils of the skin, leading to the exacerbation of the disease outcome [42]. Conversely, the presence of antibodies against the salivary proteins of VL sand fly vector has resulted in protection in humans and dogs [78,79,75].…”

“…After identification of the protection, it is important to know which salivary proteins are responsible for this protective immunity. The low number and low complication of approximately 30 salivary proteins have made it possible to screen for the salivary proteins accountable for a DTH-Th1 response in several sand fly species [42]. The first sand fly species for which the protective salivary proteins were identified was P. papatasi and the protein was called PpSP15.…”

“…Conversely, the presence of antibodies against the salivary proteins of VL sand fly vector has resulted in protection in humans and dogs [78,79,75]. Antibodies are believed to neutralize the salivary proteins which can have an effect on hemostasis, therefore preventing the migration of the infected cells to the peripheral circulation and then to liver, spleen and bone marrow [42]. The protection against leishmaniasis has been acquired when experimental hosts were immunized by salivary gland homogenate (SGH) or were repeatedly bitten by the sand fly and then were challenged with SGH of the same sand fly species and Leishmania parasites.…”

“…The sand fly saliva has immunomodulatory characteristics and induces specific immune responses including antibody production and cellular immune responses. All examined vector species in the Old and New World have shown to produce immune responses in their vertebrate hosts [42]. The saliva of sand fly is known to enhance Leishmania infection.…”

“…Although to mimic Leishmania transmission in nature, it would be better to use the Leishmania-infected sand fly challenge, this kind of experiments are scarce and most studies are conducted with the needle injections of SGH plus Leishmania parasites [41]. sand fly biting, there is a close proximity between the parasite and the salivary proteins , in the microenvironment of the host skin where anti-saliva DTH responses will interfere with the parasite establishment [42]. After identification of the protection, it is important to know which salivary proteins are responsible for this protective immunity.…”