Phenotypic and functional analyses of NK and NKT-like populations during the early stages of chikungunya infection

Abstract

The aim of this study was to characterize NK (CD56+CD3−) and NKT-like cell (CD56+CD3+) responses early after chikungunya infection. Expression profiling and functional analysis of T/NK/NKT-like cells were performed on samples from 56 acute and 31 convalescent chikungunya patients and 56 control individuals. The percentages of NK cells were high in both patient groups, whereas NKT-like cell percentages were high only in the convalescent group. The percentages of NKp30+CD3−CD56+, NKp30+CD3+CD56+, CD244+CD3−CD56+, and CD244+CD3+CD56+cells were high, whereas the percentages of NKG2D+CD3−CD56+ and NKG2D+CD3+CD56+cells were low in both patient groups. The percentages of NKp44+CD3−CD56+ cells were high in both patient groups, whereas the percentages of NKp44+CD3+CD56+ cells were higher in the acute group than in convalescent and control groups. The percentages of NKp46+CD3−CD56+ cells were high in both patient groups. Higher percentages of perforin+CD3−CD56+ and perforin+CD3+CD56+ cells were observed in acute and convalescent patients, respectively. Higher cytotoxic activity was observed in acute patients than in controls. IFN-γ expression on NK cells of convalescent patients and on NKT-like cells of both patient groups was indicative of the regulatory role of NK and NKT-like cells. Collectively, these data showed that higher expression of activating receptors on NK/NKT-like cells and perforin+ NK cells in acute patients could be responsible for increased cytotoxicity. The observed expression of perforin+ NK cells in the acute phase and IFN-γ+ NKT-like cells in the subsequent convalescent stage showed that NK/NKT-like cells mount an early and efficient response to chikungunya virus. Further study of the molecular mechanisms that limit viral dissemination/establishment of chronic disease will aid in understanding how NK/NKT-like cells control chikungunya infection.

Pathogenic Th1 responses in CHIKV‐induced inflammation and their modulation upon Plasmodium parasites co‐infection

“…Upregulation of IL‐12, a potent NK cell stimulator, has been reported in joints of virus‐infected mice suggesting the involvement of activated NK cells. Moreover, a rapid expansion of NK cells and increased cytotoxic activity during the acute phase of CHIKF have been observed in a patient cohort . Some insights on the function of NK cells in CHIKV‐induced swelling have also been observed in one of our studies .…”

“…Moreover, a rapid expansion of NK cells and increased cytotoxic activity during the acute phase of CHIKF have been observed in a patient cohort. 43,44 Some insights on the function of NK cells in CHIKV-induced swelling have also been observed in one of our studies. 16 Particularly, the more severe early acute joint swelling induced by La Réunion LR2006 OPY1 isolate as compared to the Caribbean CNR20235 isolate was associated with a higher and intensive NK cell activity during the early stages of the immune response in mouse joints.…”

Review: Chikungunya Arthritis: Implications of Acute and Chronic Inflammation Mechanisms on Disease Management

“…In addition to a potent type I IFN response, the acute stage of chikungunya virus infection (<21 days after the onset of infection) is associated with elevated patient plasma levels of multiple soluble factors, including proinflammatory cytokines and chemokines (CCL2, macrophage migration inhibitory factor, CCL4, CXCL10, IL‐6, IL‐8, and IL‐16), antiinflammatory cytokines (IL‐1 receptor A, IL‐10, and IL‐13), growth factors (granulocyte colony‐stimulating factor [G‐CSF], granulocyte–macrophage colony‐stimulating factor [GM‐CSF], vascular endothelial growth factor, and stem cell growth factor β) and other mediators (IFNγ, IL‐4, IL‐7, and CXCL9) . This results in intense monocyte trafficking to the infected tissues , along with strong activation of both CD8+ T and natural killer (NK) cells to assist in clearing the virus . The post‐acute stage of chikungunya virus (from the fourth week to the third month after the onset of infection) is characterized by very polymorphous manifestations prolonging the initial inflammatory symptoms (acute arthritis) by diverse rheumatic disorders, including periarticular involvement, slowly regressive enthesitis, tenosynovitis, and bursitis, together with nonrheumatic and systemic symptoms .…”

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

“…The impact of natural killer T (NKT) cells in CHIKV infection is less well-understood. In patients, acute CHIKV infection resulted in an increase of NKT cells in the blood (54). These NKT cells were found to upregulate the expression of IFN-γ, but not perforin.…”