regulation of global gene expression in human loa loa infection is a function of chronicity监管全球基因表达在人类贷款贷款感染是慢性的函数.pdfVIP

Regulation of Global Gene Expression in Human Loa loa Infection Is a Function of Chronicity 1 2¤ 1 Cathy Steel *, Sudhir Varma , Thomas B. Nutman 1 Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America, 2 Bioinformatics and Computational Biology Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America Abstract Background: Human filarial infection is characterized by downregulated parasite-antigen specific T cell responses but distinct differences exist between patients with longstanding infection (endemics) and those who acquired infection through temporary residency or visits to filarial-endemic regions (expatriates). Methods and Findings: To characterize mechanisms underlying differences in T cells, analysis of global gene expression using human spotted microarrays was conducted on CD4+ and CD8+ T cells from microfilaremic Loa loa-infected endemic and expatriate patients. Assessment of unstimulated cells showed overexpression of genes linked to inflammation and caspase-associated cell death, particularly in endemics, and enrichment of the Th1/Th2 canonical pathway in endemic CD4+ cells. However, pathways within CD8+ unstimulated cells were most significantly enriched in both patient groups. Antigen (Ag)-driven gene expression was assessed to microfilarial Ag (MfAg) and to the nonparasite Ag streptolysin O (SLO). For MfAg-driven cells, the number of genes differing significantly from unstimulated cells was greater in endemics compared to expatriates (p,0.0001). Functional analysis showed a differential increase in genes associated with