Abstract
BackgroundInfection by chikungunya (CHIKV) and dengue virus (DENV) can cause a wide spectrum of clinical features, many of which are undifferentiated. Cytokines, which broadly also include chemokines and growth factors, have been shown to play a role in protective immunity as well as DENV and CHIKV pathogenesis. However, differences in cytokine response to both viruses remain poorly understood, especially in patients from countries where both viruses are endemic. Our study is therefore aimed to provide a comparative profiling of cytokine response induced by acute DENV and CHIKV infections in patients with similar disease stages and in experimental in vitro infections.MethodsBy using multiplex immunoassay, we compared host cytokine profiles between acute CHIKV and DENV infections by analysing serum cytokine levels of IL-1α, IL-4, IL-5, IL-8, IL-13, RANTES, MCP-3, eotaxin, PDGF-AB/BB, and FGF-2 from the sera of acute chikungunya and dengue fever patients. We further investigated the cytokine profile responses using experimental in vitro CHIKV and DENV infections of peripheral blood mononuclear cells (PBMCs).ResultsWe found that both CHIKV and DENV-infected patients had an upregulated level of IL-8 and IL-4, with the highest IL-4 level observed in DENV-2 infected patients. Higher IL-8 level was also correlated with lower platelet count in dengue patients. IL-13 and MCP-3 downregulation was observed only in chikungunya patients, while conversely PDGF-AB/BB and FGF-2 downregulation was unique in dengue patients. Age-associated differential expression of IL-13, MCP-3, and IL-5 was also observed, while distinct kinetics of IL-4, IL-8, and FGF-2 expression between CHIKV and DENV-infected patients were identified. Furthermore, the unique pattern of IL-8, IL-13 and MCP-3, but not IL-4 expression was also recapitulated using experimental in vitro infection in PBMCs.ConclusionsTaken together, our study identified common cytokine response profile characterized by upregulation of IL-8 and IL-4 between CHIKV and DENV infection. Downregulation of IL-13 and MCP-3 was identified as a unique cytokine response profile of acute CHIKV infection, while distinct downregulation of PDGF-AB/BB and FGF-2 characterized the response from acute DENV infection. Our study provides an important overview of the host cytokine responses between CHIKV and DENV infection, which is important to further understand the mechanism and pathology of these diseases.
Highlights
Infection by chikungunya (CHIKV) and dengue virus (DENV) can cause a wide spectrum of clinical features, many of which are undifferentiated
Taken together, our study identified common cytokine response profile characterized by upregulation of IL-8 and IL-4 between Chikungunya virus (CHIKV) and DENV infection
Downregulation of IL-13 and MCP-3 was identified as a unique cytokine response profile of acute CHIKV infection, while distinct downregulation of PDGF-AB/BB and FGF-2 characterized the response from acute DENV infection
Summary
Infection by chikungunya (CHIKV) and dengue virus (DENV) can cause a wide spectrum of clinical features, many of which are undifferentiated. Chikungunya virus (CHIKV) is another mosquito-borne single positive-stranded RNA virus of the family Togaviridae, genus Alphavirus, which infects millions of people annually, contributing to widespread morbidity and explosive outbreaks of debilitating polyarthralgia [2]. Patients infected with either virus can be asymptomatic or present with an undifferentiated febrile illness beginning 3−10 days after infection, with symptoms such as arthralgia, myalgia, headache, rash, and/or nausea [2] Such similarities can be problematic as CHIKV infection is often mistakenly diagnosed as the more common dengue fever, especially in areas where both viruses cocirculate. Chikungunya fever cases have often been found in presumptive dengue cases or during dengue outbreaks when laboratory confirmation was performed [3,4,5]
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