Differential inhibitory and activating NK cell receptor levels and NK/NKT-like cell functionality in chronic and recovered stages of chikungunya

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.

Cellular and Molecular Immune Response to Chikungunya Virus Infection

“…In contrast, compared to controls, NK and NKT-like (CD3 + CD56 + ) cells had lower cytotoxicity and higher expression of IFN-γ in the chronic phase. In addition, more of these cells expressed the inhibitory NKG2A receptor, while fewer were positive for the activating NKG2D (Thanapati et al, 2017 ).…”

Effectiveness ofHaemophilus influenzaetype b vaccination after splenectomy - impact on selected immunological parameters

“…35,36 NKT cells recognize glycolipid antigens, such as glycosylceramides, present in the cell wall of Gram-negative bacteria. [37][38][39] NKT cells can recognize lipid antigens and thus broaden the repertoire of antigens recognized by conventional T cells. In addition, in spite of the limited diversity of T-cell receptors (TCR) in NKT cells, they recognize many different microorganism antigens, which points to the high plasticity of their TCRs.…”

Role of T Cells in Chikungunya Virus Infection and Utilizing Their Potential in Anti-Viral Immunity

“…In chronic patients, NKT cell levels were significantly lower than healthy controls (55), although they still upregulated IFN-γ expression. In contrast, the expression levels of IFN-γ and TNFα by NKT cells in convalescent patients are similar to that of healthy controls (54,55).…”