title: Cytokine responses to novel antigens in a peri-urban population in Brazil exposed to Leishmania infantum chagasi.
abstract: Visceral leishmaniasis (VL) is fatal if untreated, and there are no vaccines for this disease. High levels of CD4-derived interferon-γ (IFN-γ) in the presence of low levels of interleukin-10 (IL-10) predicts vaccine success. Tumor necrosis factor-α (TNF-α) is also important in this process. We characterized human immune responses in three groups exposed to Leishmania infantum chagasi in Brazil: 1) drug-cured VL patients (recovered VL); 2) asymptomatic persons with positive Leishmania-specific delayed-type hypersensitivity skin reactions (DTH+); and 3) DTH-negative household contacts. Magnitude of DTH correlated with crude Leishmania antigen-driven IFN-γ, TNF-α, and IL-5, but not IL-10. DTH+ persons showed equivalent levels of IFN-γ, but higher levels of IL-10, to tryparedoxin peroxidase and Leishmania homolog of receptor for activated C kinase compared with recovered VL patients. The IFN-γ:IL-10 and TNF-α:IL-10 ratios were higher in recovered VL patients than in DTH+ persons. Seven of 11 novel candidates (R71, L37, N52, L302.06, M18, J41, and M22) elicited cytokine responses (36-71% of responders) in recovered VL patients and DTH+ persons. This result confirmed their putative status as cross-species vaccine/immunotherapeutic candidates.
authors: Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom. c.stober@doctors.org.uk
authors: Carmel B
authors: CB
authors: Stober
authors: Selma M B
authors: SM
authors: Jeronimo
authors: Nubia N
authors: NN
authors: Pontes
authors: E Nancy
authors: EN
authors: Miller
authors: Jenefer M
authors: JM
authors: Blackwell
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D001938:Brazil; D016207:Cytokines / Q000276:immunology*; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D018314:Leishmania infantum / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology* / Q000469:parasitology / Q000503:physiopathology; D010544:Peroxidases / Q000276:immunology; D015800:Protozoan Proteins / Q000276:immunology; D014505:Urban Population
chemical_list: D000953:Antigens, Protozoan; D016207:Cytokines; D015800:Protozoan Proteins; D010544:Peroxidases; C110959:tryparedoxin peroxidase