No abstract

Regulatory T (Treg) cells hold centre stage in regulating the immune responses in most viral infections. However, their involvement in chikungunya infection is unexplored. In the current study, the frequencies and functionality of peripheral Treg and T effector (Teff) cells were assessed during different phases of chikungunya by flow cytometry and in-vitro cytokine assays. Treg cells were also studied in rheumatoid arthritis (RA) patients, whose symptoms closely mimic chronic chikungunya arthritis patients. Frequency of Treg cells was lower in acute and chronic chikungunya arthritis patients than in recovered individuals and controls, and comparable among recovered individuals and controls. Treg/Teff ratio was lower in acute than in chronic chikungunya arthritis patients, recovered individuals and controls. Higher secretion of CHIKV specific IL-10 was observed in recovered individuals than in acute, chronic chikungunya arthritis patients and controls. Frequencies of Treg and Teff cells were higher and Treg/Teff ratio was lower in RA patients than in chronic chikungunya arthritis patients. The results indicate that reduction of Treg cells was associated with ongoing CHIKV infection and normalization of Treg cells with resolution of disease. Contrasting phenotypic data in RA and chronic chikungunya arthritis suggest an altogether different mechanism of Treg-mediated pathology in both arthritis conditions. Overall, our preliminary study, suggesting an association of peripheral Treg cells and IL-10 with recovery from chikungunya, may provide insight into chikungunya disease prognosis and warrants further study.

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.

Chikungunya, caused by the chikungunya virus (CHIKV) mostly presents as acute and chronic articular inflammatory manifestations. Interleukin 1 receptor antagonist (IL-1RN) is a potent endogenous competitive inhibitor of IL-1α and 1β and has an antiinflammatory role. The present study evaluated the possible association of IL1RN variable number tandem-repeat (VNTR) alleles and genotypes, and CHIKV stimulated IL-1RN cytokine production with resistance and/or susceptibility to chikungunya infection and disease state in 224 patients with chikungunya (61 patients with acute chikungunya and 163 patients with chronic chikungunya) and 355 healthy controls.Polymerase chain reaction, CHIKV stimulated cytokine assay and luminex platform were used for assessing polymorphism and protein levels respectively. The study revealed a significant association of IL1RN*1/*1 genotype under recessive genetic model with the risk of developing chikungunya infection. Our findings also indicated that IL1RN *2 allele under dominant mode was associated with protection to chronic chikungunya. The results also revealed a higher production of IL-1 RN protein in patients with chronic chikungunya. To conclude, the results suggest the association of ILRN VNTR polymorphism and IL-RN protein levels with chronic chikungunya.