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

Adeline S L Yeo, Nur Atiqah Azhar, Wanyi Yeow, C. Conover Talbot, Mohammad Asif Khan, Esaki M. Shankar, Anusyah Rathakrishnan, Azliyati Azizan, Seok Mui Wang, Siew Kim Lee, Mun Yik Fong, Rishya Manikam, Shamala Devi Sekaran

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Objectives: 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. Methods: 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. Results: 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. Conclusion: 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.

Original languageEnglish
Article numberA1295
JournalPLoS One
Volume9
Issue number4
DOIs
Publication statusPublished - Apr 11 2014
Externally publishedYes

Fingerprint

Asymptomatic Infections
dengue
Dengue
Up-Regulation
Down-Regulation
Genes
Interleukin-8
genes
stromelysin 2
Interleukin-9
Disease Vectors
Chemokine CCL5
Interleukin-18
Interleukin-13
Interleukin-5
Immunologic Factors
Metalloproteases
metalloproteinases
Infection
Neutralizing Antibodies

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Lack of clinical manifestations in asymptomatic dengue infection is attributed to broad down-regulation and selective up-regulation of host defence response genes. / Yeo, Adeline S L; Azhar, Nur Atiqah; Yeow, Wanyi; Talbot, C. Conover; Khan, Mohammad Asif; Shankar, Esaki M.; Rathakrishnan, Anusyah; Azizan, Azliyati; Wang, Seok Mui; Lee, Siew Kim; Fong, Mun Yik; Manikam, Rishya; Sekaran, Shamala Devi.

In: PLoS One, Vol. 9, No. 4, A1295, 11.04.2014.

Research output: Contribution to journalArticle

Yeo, ASL, Azhar, NA, Yeow, W, Talbot, CC, Khan, MA, Shankar, EM, Rathakrishnan, A, Azizan, A, Wang, SM, Lee, SK, Fong, MY, Manikam, R & Sekaran, SD 2014, 'Lack of clinical manifestations in asymptomatic dengue infection is attributed to broad down-regulation and selective up-regulation of host defence response genes', PLoS One, vol. 9, no. 4, A1295. https://doi.org/10.1371/journal.pone.0092240
Yeo, Adeline S L ; Azhar, Nur Atiqah ; Yeow, Wanyi ; Talbot, C. Conover ; Khan, Mohammad Asif ; Shankar, Esaki M. ; Rathakrishnan, Anusyah ; Azizan, Azliyati ; Wang, Seok Mui ; Lee, Siew Kim ; Fong, Mun Yik ; Manikam, Rishya ; Sekaran, Shamala Devi. / Lack of clinical manifestations in asymptomatic dengue infection is attributed to broad down-regulation and selective up-regulation of host defence response genes. In: PLoS One. 2014 ; Vol. 9, No. 4.
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AU - Azhar, Nur Atiqah

AU - Yeow, Wanyi

AU - Talbot, C. Conover

AU - Khan, Mohammad Asif

AU - Shankar, Esaki M.

AU - Rathakrishnan, Anusyah

AU - Azizan, Azliyati

AU - Wang, Seok Mui

AU - Lee, Siew Kim

AU - Fong, Mun Yik

AU - Manikam, Rishya

AU - Sekaran, Shamala Devi

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N2 - Objectives: 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. Methods: 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. Results: 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. Conclusion: 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.

AB - Objectives: 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. Methods: 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. Results: 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. Conclusion: 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.

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