Lack of clinical manifestations in asymptomatic dengue infection is attributed to broad down-regulation and selective up-regulation of host defence response genes

• Published in: PloS one Vol. 9; no. 4; p. e92240
• Main Authors: Yeo, Adeline S L, Azhar, Nur Atiqah, Yeow, Wanyi, Talbot, Jr, C Conover, Khan, Mohammad Asif, Shankar, Esaki M, Rathakrishnan, Anusyah, Azizan, Azliyati, Wang, Seok Mui, Lee, Siew Kim, Fong, Mun Yik, Manikam, Rishya, Devi Sekaran, Shamala
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01-04-2014; Public Library of Science (PLoS)
• Subjects: Antibodies; Antibodies, Neutralizing - metabolism; Bioinformatics; Biology and Life Sciences; CD28 antigen; CD80 antigen; Cytokines; Cytokines - metabolism; Dengue; Dengue - virology; Dengue fever; Dengue Virus - pathogenicity; Development and progression; Down-Regulation; Family medical history; Female; Gene expression; Gene regulation; Genes; Genetic aspects; Growth factors; Health aspects; Hepatitis; Hospitals; Households; Humans; Immune response; Immunology; Immunopathogenesis; Infections; Infectious diseases; Interleukin 1; Interleukin 10; Interleukin 13; Interleukin 18; Interleukin 2; Interleukin 3; Interleukin 4; Interleukin 5; Interleukin 8; Interleukin 9; Male; Matrix metalloproteinase; Matrix Metalloproteinases - metabolism; Medicine; Medicine and Health Sciences; Metalloproteinase; Mosquitoes; Neutrophil collagenase; Patients; Permeability; Physiological aspects; Plasma; RANTES; Signal Transduction; Stromelysin 2; Studies; Tissue inhibitor of metalloproteinase 1; TNF inhibitors; Transforming growth factor-b; Tumor necrosis factor; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; University graduates; Up-regulation; Vector-borne diseases; Viral diseases; Virology; Viruses; United States; Malaysia; Kuala Lumpur Malaysia; United States > US; Maryland; Baltimore Maryland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0092240

Dengue represents one of the most serious life-threatening vector-borne infectious diseases that afflicts approximately 50 million people across the globe annually. Whilst symptomatic infections are frequently reported, asymptomatic dengue remains largely unnoticed. Therefore, we sought to investigate the immune correlates conferring protection to individuals that remain clinically asymptomatic.
We determined the levels of neutralizing antibodies (nAbs) and gene expression profiles of host immune factors in individuals with asymptomatic infections, and whose cognate household members showed symptoms consistent to clinical dengue infection.
We observed broad down-regulation of host defense response (innate, adaptive and matrix metalloprotease) genes in asymptomatic individuals as against symptomatic patients, with selective up-regulation of distinct genes that have been associated with protection. Selected down-regulated genes include: TNF α (TNF), IL8, C1S, factor B (CFB), IL2, IL3, IL4, IL5, IL8, IL9, IL10 and IL13, CD80, CD28, and IL18, MMP8, MMP10, MMP12, MMP15, MMP16, and MMP24. Selected up-regulated genes include: RANTES (CCL5), MIP-1α (CCL3L1/CCL3L3), MIP-1β (CCL4L1), TGFβ (TGFB), and TIMP1.
Our findings highlight the potential association of certain host genes conferring protection against clinical dengue. These data are valuable to better explore the mysteries behind the hitherto poorly understood immunopathogenesis of subclinical dengue infection.