| T-bet, GATA-3, and Foxp3 expression and Th1/Th2 cytokine production in the clinical outcome of human infection with Leishmania (Viannia) species. | |
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MedLine Citation:
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PMID: 20583921 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: T cell differentiation determines susceptibility and resistance to experimental cutaneous leishmaniasis, yet mixed T1/Th2 responses characterize the clinical spectrum of human infection with Leishmania (Viannia) species. MATERIALS AND METHODS: To discern the interrelationship of T cell differentiation and outcome of human infection, we examined factors that regulate T cell differentiation and Th1/Th2 cytokine responses in asymptomatic infection, active and historical chronic and recurrent cutaneous leishmaniasis. T-bet, GATA-3, Foxp3, and cytokine gene expression were quantified by real-time polymerase chain reaction and correlated with interleukin 2, interferon gamma, tumor necrosis factor alpha, interleukin 4, interleukin 13, and interleukin 10 secretion during in vitro response to live Leishmania panamensis. RESULTS: Higher GATA-3 expression than T-bet expression occurred throughout the 15 days of coculture with promastigotes; however, neither transcription nor secretion of interleukin 4 was detected. A sustained inverse correlation between GATA-3 expression and secretion of proinflammatory cytokines interferon gamma and tumor necrosis factor alpha was observed in asymptomatic infection. In contrast, higher T-bet expression and a higher ratio of T-bet to GATA-3 characterized active recurrent disease. Down-regulation of T-bet and GATA-3 expression and increased interleukin 2 secretion, compared with control subjects, was directly correlated with Foxp3 expression and interleukin 13 secretion in chronic disease. CONCLUSIONS: Regulation of the inflammatory response rather than biased Th1/Th2 response distinguished asymptomatic and recalcitrant outcomes of infection with Leishmnania viannia species. |
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Authors:
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Yira Rosalba Díaz; Ricardo Rojas; Liliana Valderrama; Nancy Gore Saravia |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of infectious diseases Volume: 202 ISSN: 1537-6613 ISO Abbreviation: J. Infect. Dis. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-05 Completed Date: 2010-07-20 Revised Date: 2011-04-27 |
Medline Journal Info:
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Nlm Unique ID: 0413675 Medline TA: J Infect Dis Country: United States |
Other Details:
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Languages: eng Pagination: 406-15 Citation Subset: AIM; IM |
Affiliation:
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Centro Internacional de Entrenamiento e Investigaciones Médicas (CIDEIM), Cali, Colombia. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Aged Animals Coculture Techniques Cytokines / secretion* Female Forkhead Transcription Factors / biosynthesis*, genetics GATA3 Transcription Factor / biosynthesis*, genetics Gene Expression Gene Expression Profiling Humans Leishmania / immunology Leishmaniasis / immunology*, parasitology Leukocytes, Mononuclear / immunology, parasitology Male Middle Aged T-Box Domain Proteins / biosynthesis*, genetics Th1 Cells / immunology* Th2 Cells / immunology* Treatment Outcome Young Adult |
| Grant Support | |
ID/Acronym/Agency:
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1 U19AIO65866//PHS HHS; D43 TW006589/TW/FIC NIH HHS; D43 TW006589-01/TW/FIC NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/FOXP3 protein, human; 0/Forkhead Transcription Factors; 0/GATA3 Transcription Factor; 0/GATA3 protein, human; 0/T-Box Domain Proteins; 0/T-box transcription factor TBX21 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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