Date Published: November 28, 2007
Publisher: Public Library of Science
Author(s): Tatiana R. de Moura, Fabiano Oliveira, Fernanda O. Novais, José Carlos Miranda, Jorge Clarêncio, Ivonise Follador, Edgar M. Carvalho, Jesus G. Valenzuela, Manoel Barral-Netto, Aldina Barral, Cláudia Brodskyn, Camila I. de Oliveira, Charles Jaffe
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.
Partial Text: Protozoan parasites of the genus Leishmania cause a broad spectrum of diseases, collectively known as leishmaniasis, that occur predominantly in tropical and subtropical regions. The leishmaniases are transmitted by different species of sand flies, and depending on the Leishmania species involved and the genetic makeup or immunological status of the host, different clinical manifestations of the disease are observed.
The results presented herein show that L. intermedia SGS shifted the immune responses to L. braziliensis to type 2 and immunization of BALB/c mice with SGS led to enhanced L. braziliensis infection. Additionally, induction of this distinctive role played by L. intermedia saliva comes from data obtained with patients with active CL who presented higher anti-L. intermedia SGS antibody titers when compared to exposed individuals with positive anti-Leishmania DTH.