Sand fly salivary proteins induce strong cellular immunity in a natural reservoir of visceral leishmaniasis with adverse consequences for Leishmania.
Immunity to a sand fly salivary protein protects against visceral leishmaniasis (VL) in hamsters. This protection was associated with the development of cellular immunity in the form of a delayed-type hypersensitivity response and the presence of IFN-gamma at the site of sand fly bites. To date, there are no data available regarding the cellular immune response to sand fly saliva in dogs, the main reservoirs of VL in Latin America, and its role in protection from this fatal disease. Two of 35 salivary proteins from the vector sand fly Lutzomyia longipalpis, identified using a novel approach termed reverse antigen screening, elicited strong cellular immunity in dogs. Immunization with either molecule induced high IgG(2) antibody levels and significant IFN-gamma production following in vitro stimulation of PBMC with salivary gland homogenate (SGH). Upon challenge with uninfected or infected flies, immunized dogs developed a cellular response at the bite site characterized by lymphocytic infiltration and IFN-gamma and IL-12 expression. Additionally, SGH-stimulated lymphocytes from immunized dogs efficiently killed Leishmania infantum chagasi within autologous macrophages. Certain sand fly salivary proteins are potent immunogens obligatorily co-deposited with Leishmania parasites during transmission. Their inclusion in an anti-Leishmania vaccine would exploit anti-saliva immunity following an infective sand fly bite and set the stage for a protective anti-Leishmania immune response.
Collin
Nicolas
N
Vector Molecular Biology Unit, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Gomes
Regis
R
Teixeira
Clarissa
C
Cheng
Lily
L
Laughinghouse
Andre
A
Ward
Jerrold M
JM
Elnaiem
Dia-Eldin
DE
Fischer
Laurent
L
Valenzuela
Jesus G
JG
Kamhawi
Shaden
S
D000818:Animals; D000917:Antibody Formation; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003627:Data Interpretation, Statistical; D004285:Dogs; D005260:Female; D015870:Gene Expression; D006968:Hypersensitivity, Delayed; D007111:Immunity, Cellular; D007299:Insect Bites and Stings / Q000276:immunology; D019476:Insect Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007303:Insect Vectors / Q000235:genetics / Q000276:immunology / Q000469:parasitology; D018314:Leishmania infantum / Q000276:immunology* / Q000502:physiology; D007898:Leishmaniasis, Visceral / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology; D011576:Psychodidae / Q000235:genetics / Q000276:immunology / Q000469:parasitology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012471:Salivary Proteins and Peptides / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012867:Skin / Q000276:immunology
D016207:Cytokines; D019476:Insect Proteins; D011994:Recombinant Proteins; D012471:Salivary Proteins and Peptides