Abstract
The role of natural killer (NK; CD3-CD56+)/NKT (CD3+CD56+)-like cells in chikungunya virus (CHIKV) disease progression/recovery remains unclear. Here, we investigated the expression profiles and function of NK and NKT-like cells from 35 chronic chikungunya patients, 30 recovered individuals, and 69 controls. Percentage of NKT-like cells was low in chronic chikungunya patients. NKp30+, CD244+, DNAM-1+, and NKG2D+ NK cell percentages were also lower (MFI and/or percentage), while those of CD94+ and NKG2A+ NKT-like cells were higher (MFI and/or percentage) in chronic patients than in recovered subjects. IFN-γ and TNF-α expression on NKT-like cells was high in the chronic patients, while only IFN-γ expression on NK cells was high in the recovered individuals. Furthermore, percentage of perforin+NK cells was low in the chronic patients. Lower cytotoxic activity was observed in the chronic patients than in the controls. CD107a expression on NK and NKT-like cells post anti-CD94/anti-NKG2A blocking was comparable among the patients and controls. Upregulated inhibitory and downregulated activating NK receptor expressions on NK/NKT-like cells, lower perforin+ and CD107a+NK cells are likely responsible for inhibiting the NK and NKT-like cell function in the chronic stage of chikungunya. Therefore, deregulation of NKR expression might underlie CHIKV-induced chronicity.
Highlights
The chikungunya virus (CHIKV)is a positive-sense, single-stranded RNA virus of the Alphavirus genus belonging to the family Togaviridae [1]
Impaired functionality of natural killer (NK) cells in chronic chikungunya that limit viral dissemination/establishment of chronicity in chikungunya disease. Immune effector cells, such as NK cells, have been implicated in the early control of various viral infections; it was of interest to investigate the intrinsic association between deregulated NK cell surface receptors (NKRs) expression and lymphocyte function in both chronic patients and individuals recovered from chikungunya infection
Impairment of NK cell function in the chronic patients, irrespective of NK cell percentage being comparable with the controls, may be a specific phenomenon indicating that the functional capacity per NK cell in the chronic chikungunya patients is low
Summary
The chikungunya virus (CHIKV)is a positive-sense, single-stranded RNA virus of the Alphavirus genus belonging to the family Togaviridae [1]. CHIKV belongs to the arthritogenic group of alphaviruses transmitted through the Aedes group of mosquitoes [2,3,4]. Re-emergence of chikungunya, with higher medical complications,since 2006 in several Asian and African countries, is a significant public health concern. Chikungunya outbreaks have been reported in America and the Caribbean Islands in late 2013 [5, 6]. Chikungunya is a self-limiting disease usually resolved in acute stage, persistent joints pain lasts for several months or even years in 10–20% of patients after the initial infection [3, 7,8,9,10,11].
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