Enhanced Leishmania braziliensis infection following pre-exposure to sandfly saliva.
BACKGROUND
Sand 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.


RESULTS
BALB/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-gamma 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-gamma 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.


CONCLUSIONS
These 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.
Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Brazil.
Tatiana R
TR
de Moura
Fabiano
F
Oliveira
Fernanda O
FO
Novais
José Carlos
JC
Miranda
Jorge
J
Clarêncio
Ivonise
I
Follador
Edgar M
EM
Carvalho
Jesus G
JG
Valenzuela
Manoel
M
Barral-Netto
Aldina
A
Barral
Cláudia
C
Brodskyn
Camila I
CI
de Oliveira
D000818:Animals; D015153:Blotting, Western; D020405:Dermis / Q000276:immunology / Q000469:parasitology; D004427:Ear Diseases / Q000276:immunology / Q000469:parasitology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007892:Leishmania braziliensis / Q000276:immunology / Q000502:physiology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D011576:Psychodidae; D012463:Saliva / Q000276:immunology*
D015847:Interleukin-4; D007371:Interferon-gamma