Research article
Characterization of early host responses in adults with dengue disease
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* Corresponding author: Thomas Tolfvenstam thomas.tolfvenstam@ki.se
1 Genome Institute of Singapore, 60 Biopolis Street #02-01 Genome, Singapore, 138672, Singapore
2 Infectious Disease Unit, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, 17176, Stockholm, Sweden
3 Novartis Institute for Tropical Diseases, 10 Biopolis Road #05-01 Chromos, Singapore, 138670, Singapore
4 DUKE-NUS Graduate Medical School, 8 College Road, Singapore, 169857, Singapore
BMC Infectious Diseases 2011, 11:209 doi:10.1186/1471-2334-11-209
Published: 2 August 2011Abstract
Background
While dengue-elicited early and transient host responses preceding defervescence could shape the disease outcome and reveal mechanisms of the disease pathogenesis, assessment of these responses are difficult as patients rarely seek healthcare during the first days of benign fever and thus data are lacking.
Methods
In this study, focusing on early recruitment, we performed whole-blood transcriptional profiling on denguevirus PCR positive patients sampled within 72 h of self-reported fever presentation (average 43 h, SD 18.6 h) and compared the signatures with autologous samples drawn at defervescence and convalescence and to control patients with fever of other etiology.
Results
In the early dengue fever phase, a strong activation of the innate immune response related genes were seen that was absent at defervescence (4-7 days after fever debut), while at this second sampling genes related to biosynthesis and metabolism dominated. Transcripts relating to the adaptive immune response were over-expressed in the second sampling point with sustained activation at the third sampling. On an individual gene level, significant enrichment of transcripts early in dengue disease were chemokines CCL2 (MCP-1), CCL8 (MCP-2), CXCL10 (IP-10) and CCL3 (MIP-1α), antimicrobial peptide β-defensin 1 (DEFB1), desmosome/intermediate junction component plakoglobin (JUP) and a microRNA which may negatively regulate pro-inflammatory cytokines in dengue infected peripheral blood cells, mIR-147 (NMES1).
Conclusions
These data show that the early response in patients mimics those previously described in vitro, where early assessment of transcriptional responses has been easily obtained. Several of the early transcripts identified may be affected by or mediate the pathogenesis and deserve further assessment at this timepoint in correlation to severe disease.