Abstract
BackgroundDengue virus (DENV) is the most prominent arbovirus worldwide, causing major epidemics in South-East Asia, South America and Africa. In 2010, a major DENV-2 outbreak occurred in Gabon with cases of patients co-infected with chikungunya virus (CHIKV). Although the innate immune response is thought to be of primordial importance in the development and outcome of arbovirus-associated pathologies, our knowledge of the role of natural killer (NK) cells during DENV-2 infection is in its infancy.MethodologyWe performed the first extensive comparative longitudinal characterization of NK cells in patients infected by DENV-2, CHIKV or both viruses. Hierarchical clustering and principal component analyses were performed to discriminate between CHIKV and DENV-2 infected patients.Principal FindingsWe observed that both activation and differentiation of NK cells are induced during the acute phase of infection by DENV-2 and CHIKV. Combinatorial analysis however, revealed that both arboviruses induced two different signatures of NK-cell responses, with CHIKV more associated with terminal differentiation, and DENV-2 with inhibitory KIRs. We show also that intracellular production of interferon-γ (IFN-γ) by NK cells is strongly stimulated in acute DENV-2 infection, compared to CHIKV.Conclusions/SignificanceAlthough specific differences were observed between CHIKV and DENV-2 infections, the significant remodeling of NK cell populations observed here suggests their potential roles in the control of both infections.
Highlights
Dengue virus (DENV), the most widespread arbovirus worldwide, is transmitted by Ae. aegypti and Ae. albopictus mosquitoes and is responsible for major outbreaks causing serious health and economical problems
The clinical picture associated with acute dengue virus (DENV) infections ranges from classical febrile illness to life-threatening disease
We examine the particular role of natural killer (NK) cells in DENV infection at different time points after the onset of symptoms
Summary
Dengue virus (DENV), the most widespread arbovirus worldwide, is transmitted by Ae. aegypti and Ae. albopictus mosquitoes and is responsible for major outbreaks causing serious health and economical problems. Dengue is endemic in at least 100 countries in Southeast Asia, the pacific islands, the Americas, Africa, and the Caribbean and the World Health Organization (WHO) estimates that 50 to 100 million infections occur yearly [1,2]. Chikungunya virus (CHIKV), another arbovirus transmitted by the mosquito vectors Ae. aegypti and Ae. Albopictus, reemerged prominently in 2004 [3]. Dengue virus (DENV) is the most prominent arbovirus worldwide, causing major epidemics in South-East Asia, South America and Africa. In 2010, a major DENV-2 outbreak occurred in Gabon with cases of patients co-infected with chikungunya virus (CHIKV). The innate immune response is thought to be of primordial importance in the development and outcome of arbovirus-associated pathologies, our knowledge of the role of natural killer (NK) cells during DENV-2 infection is in its infancy.
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