PMID- 22826477 OWN - NLM STAT- MEDLINE DCOM- 20121221 LR - 20211021 IS - 1476-1645 (Electronic) IS - 0002-9637 (Print) IS - 0002-9637 (Linking) VI - 87 IP - 4 DP - 2012 Oct TI - Cytokine responses to novel antigens in a peri-urban population in Brazil exposed to Leishmania infantum chagasi. PG - 663-70 LID - 10.4269/ajtmh.2012.12-0180 [doi] AB - Visceral leishmaniasis (VL) is fatal if untreated, and there are no vaccines for this disease. High levels of CD4-derived interferon-gamma (IFN-gamma) in the presence of low levels of interleukin-10 (IL-10) predicts vaccine success. Tumor necrosis factor-alpha (TNF-alpha) 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-gamma, TNF-alpha, and IL-5, but not IL-10. DTH+ persons showed equivalent levels of IFN-gamma, 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-gamma:IL-10 and TNF-alpha: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. FAU - Stober, Carmel B AU - Stober CB AD - Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom. c.stober@doctors.org.uk FAU - Jeronimo, Selma M B AU - Jeronimo SM FAU - Pontes, Nubia N AU - Pontes NN FAU - Miller, E Nancy AU - Miller EN FAU - Blackwell, Jenefer M AU - Blackwell JM LA - eng GR - R01AI067874-01/AI/NIAID NIH HHS/United States GR - P50 AI074321/AI/NIAID NIH HHS/United States GR - P50 AI030639/AI/NIAID NIH HHS/United States GR - R01 AI067874/AI/NIAID NIH HHS/United States GR - P50AI-30639/AI/NIAID NIH HHS/United States GR - R01 AI076233/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20120723 PL - United States TA - Am J Trop Med Hyg JT - The American journal of tropical medicine and hygiene JID - 0370507 RN - 0 (Antigens, Protozoan) RN - 0 (Cytokines) RN - 0 (Protozoan Proteins) RN - EC 1.11.1.- (Peroxidases) RN - EC 1.11.1.- (tryparedoxin peroxidase) SB - IM MH - Animals MH - Antigens, Protozoan/*immunology MH - Brazil MH - Cytokines/*immunology MH - Humans MH - Hypersensitivity, Delayed/immunology MH - Leishmania infantum/*immunology MH - Leishmaniasis, Visceral/*immunology/parasitology/physiopathology MH - Peroxidases/immunology MH - Protozoan Proteins/immunology MH - *Urban Population PMC - PMC3516316 EDAT- 2012/07/25 06:00 MHDA- 2012/12/22 06:00 PMCR- 2013/10/03 CRDT- 2012/07/25 06:00 PHST- 2012/07/25 06:00 [entrez] PHST- 2012/07/25 06:00 [pubmed] PHST- 2012/12/22 06:00 [medline] PHST- 2013/10/03 00:00 [pmc-release] AID - ajtmh.2012.12-0180 [pii] AID - 10.4269/ajtmh.2012.12-0180 [doi] PST - ppublish SO - Am J Trop Med Hyg. 2012 Oct;87(4):663-70. doi: 10.4269/ajtmh.2012.12-0180. Epub 2012 Jul 23.