Enhanced Leishmania braziliensis Infection Following Pre-Exposure to Sandfly Saliva

Abstract

BackgroundSand fly saliva has an array of pharmacological and immunomodulatory components, and immunity to saliva protects against Leishmania infection. In the present study, we have studied the immune response against Lutzomyia intermedia saliva, the main vector of Leishmania braziliensis in Brazil, and the effects of saliva pre-exposure on L. braziliensis infection employing an intradermal experimental model.Methodology/principal findingsBALB/c mice immunized with L. intermedia salivary gland sonicate (SGS) developed a saliva-specific antibody response and a cellular immune response with presence of both IFN-γ and IL-4. The inflammatory infiltrate observed in SGS-immunized mice was comprised of numerous polymorphonuclear and few mononuclear cells. Mice challenged with live L. braziliensis in the presence of saliva were not protected although lesion development was delayed. The inoculation site and draining lymph node showed continuous parasite replication and low IFN-γ to IL-4 ratio, indicating that pre-exposure to L. intermedia saliva leads to modulation of the immune response. Furthermore, in an endemic area of cutaneous leishmaniasis, patients with active lesions displayed higher levels of anti-L. intermedia saliva antibodies when compared to individuals with a positive skin test result for Leishmania.ConclusionThese results show that pre-exposure to sand fly saliva plays an important role in the outcome of cutaneous leishmaniasis, in both mice and humans. They emphasize possible hurdles in the development of vaccines based on sand fly saliva and the need to identify and select the individual salivary candidates instead of using whole salivary mixture that may favor a non-protective response.

Characterization of the Antibody Response to the Saliva of Phlebotomus papatasi in People Living in Endemic Areas of Cutaneous Leishmaniasis

“…We (H. Louzir, IPSOS V) and others 17 formerly showed that the presence of salivary antibodies constitutes a risk factor for the development of ZCL. We, thus, focused our analysis on children who were negative for LST at the beginning of our study and who did not have any clinical evidence of previous ZCL.…”

Cutaneous Leishmaniasis: Update on Vaccine Development

“…58 In contrast, L intermedia salivary gland sonicate failed to control L braziliensis infection and even increased disease progression due to low IFN-γ to IL-4 ratio. 59 These conflicting results suggest that (1) salivary gland components have the ability to change the immune response of mice by either increasing susceptibility or resistance and (2) use of sandfly saliva components may not be a suitable strategy for all strains of Leishmania. Because leishmanization seems to be an effective procedure that does not involve the sandfly, sandfly components may not be essential to the development of an effective Leishmania vaccine but may still be useful against certain strains of Leishmania.…”

Sand fly saliva: toward a vaccine against leishmaniases

“…Anti-saliva antibodies have been associated with increased risk of CL caused by L. major, L. tropica and Leishmania braziliensis in Tunisia, Turkey and Brazil, accordingly [76,68,77]. 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].…”