Abstract
BackgroundPrevious works showed that immunization with saliva from Lutzomyia intermedia, a vector of Leishmania braziliensis, does not protect against experimental infection. However, L. braziliensis is also transmitted by Lutzomyia whitmani, a sand fly species closely related to Lu. intermedia. Herein we describe the immune response following immunization with Lu. whitmani saliva and the outcome of this response after L. braziliensis infection.Methods and findingsBALB/c mice immunized with Lu. whitmani saliva developed robust humoral and cellular immune responses, the latter characterized by an intense cellular infiltrate and production of IFN-γ and IL-10, by both CD4+ and CD8+ cells. Mice immunized as above and challenged with L. braziliensis plus Lu. whitmani saliva displayed significantly smaller lesions and parasite load at the challenge site. This protection was associated with a higher (p<0.05) IFN-γ production in response to SLA stimulation. Long-term persisting immunity was also detected in mice immunized with Lu. whitmani saliva. Furthermore, individuals residing in an endemic area for cutaneous leishmaniasis (CL) presented antibody responses to Lu. whitmani saliva. However CL patients, with active lesions, displayed a lower humoral response to Lu. whitmani saliva compared to individuals with subclinical Leishmania infection.ConclusionPre-exposure to Lu. whitmani saliva induces protection against L. braziliensis in a murine model. We also show that Lu. whitmani salivary proteins are immunogenic in naturally exposed individuals. Our results reinforce the importance of investigating the immunomodulatory effect of saliva from different species of closely related sand flies.
Highlights
Leishmaniasis develops when an infected sand fly bites the skin of the mammalian host, injecting saliva and the infective forms of Leishmania
We show that Lu. whitmani salivary proteins are immunogenic in naturally
We evaluated whether a delayed-type hypersensitivity response (DTH) reaction, a proxy for cellular immunity, developed in mice immunized with Lu. whitmani SGS as this effect has been shown for SGS from other sand fly species [3] and for defined salivary proteins [9]
Summary
Leishmaniasis develops when an infected sand fly bites the skin of the mammalian host, injecting saliva and the infective forms of Leishmania. Experimental co-inoculation of sand fly saliva and Leishmania sp. Mice exposed to bites of uninfected sand flies [7,8] or immunized with specific salivary molecules [9,10] were protected against Leishmania infection. In these studies, protection against disease correlated with an intense recruitment of lymphocytes and macrophages to the infection site as well as production of IFN-γ and IL-12. Previous works showed that immunization with saliva from Lutzomyia intermedia, a vector of Leishmania braziliensis, does not protect against experimental infection. We describe the immune response following immunization with Lu. whitmani saliva and the outcome of this response after L. braziliensis infection.
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