Article
Immunity to a salivary protein of a sand fly vector protects against the fatal outcome of visceral leishmaniasis in a hamster model
Registro en:
GOMES, R. et al. Immunity to a salivary protein of a sand fly vector protects against the fatal outcome of visceral leishmaniasis in a hamster model. Proceedings of the National Academy of Sciences of the United States of America, v.105, n.22, p.7845-7850, jun. 2008.
0027-8424
Autor
Gomes, Regis Bernardo Brandim
Teixeira, Clarissa Romero
Teixeira, Maria Jânia
Oliveira, Fabiano
Menezes, Maria José
Silva, Claire
Oliveira, Camila Indiani de
Miranda, José Carlos
Elnaiem, Dia-Eldin A
Kamhawi, Shaden
Valenzuela, Jesus G
Brodskyn, Claudia Ida
Resumen
Agradecimentos a Dra. Aldina Barral, Dr. Manoel Barral Netto, Dr. MC José Ribeiro, e Ryan Jochim pela revisão crítica deste manuscrito; Ao Dr. Robert Gwadz pelo apoio contínuo; a Sheila Dreher pela construção de DNA dos plasmídeos; Edivaldo Passos pela assistência técnica, e Nancy Shulman pela assistência editorial. Estudo financiado pela Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ) e Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Capes) e em parte pela Divisão de Pesquisa do Instituto Nacional de Alergia e Doenças Infecciosas e dos Institutos Nacionais da Saúde. Visceral leishmaniasis (VL) is a fatal disease for humans, and no vaccine is currently available. Sand fly salivary proteins have been associated with protection against cutaneous leishmaniasis. To test
whether vector salivary proteins can protect against VL, a hamster model was developed involving intradermal inoculation in the ears
of 100,000 Leishmania infantum chagasi parasites together with Lutzomyia longipalpis saliva to mimic natural transmission by sand
flies. Hamsters developed classical signs of VL rapidly, culminating in a fatal outcome 5–6 months postinfection. Saliva had no effect
on the course of infection in this model. Immunization with 16 DNA plasmids coding for salivary proteins of Lu. longipalpis resulted in the identification of LJM19, a novel 11-kDa protein, that protected hamsters against the fatal outcome of VL. LJM19-immunized hamsters maintained a low parasite load that correlated with an overall high IFN- /TGF- ratio and inducible NOS expression in the spleen and liver up to 5 months postinfection. Importantly, a delayed-type
hypersensitivity response with high expression of IFN- was also noted in the skin of LJM19-immunized hamsters 48 h after exposure to uninfected sand fly bites. Induction of IFN- at the site of bite could partly explain the protection observed in the viscera of LJM19-immunized hamsters through direct parasite killing and/or priming of anti-Leishmania immunity. We have shown that immunity to a defined salivary protein (LJM19) confers powerful protection
against the fatal outcome of a parasitic disease, which reinforces the concept of using components of arthropod saliva in
vaccine strategies against vector-borne diseases.