MAIT cells are activated in acute Dengue virus infection and after in vitro Zika virus infection

Dengue virus (DENV) and Zika virus (ZIKV) are members of the Flaviviridae and are predominantly transmitted via mosquito bites. Both viruses are responsible for a growing number of infections in tropical and subtropical regions. DENV infection can cause lethargy with severe morbidity and dengue shock syndrome leading to death in some cases. ZIKV is now linked with Guillain-Barré syndrome and fetal malformations including microcephaly and developmental disorders (congenital Zika syndrome). The protective and pathogenic roles played by the immune response in these infections is unknown. Mucosal-associated invariant T (MAIT) cells are a population of innate T cells with potent anti-bacterial activity. MAIT cells have also been postulated to play a role in the immune response to viral infections. In this study, we evaluated MAIT cell frequency, phenotype, and function in samples from subjects with acute and convalescent DENV infection. We found that in acute DENV infection, MAIT cells had elevated co-expression of the activation markers CD38 and HLA-DR and had a poor IFNγ response following bacterial stimulation. Furthermore, we found that MAIT cells can produce IFNγ in response to in vitro infection with ZIKV. This MAIT cell response was independent of MR1, but dependent on IL-12 and IL-18. Our results suggest that MAIT cells may play an important role in the immune response to Flavivirus infections.

登革病毒（Dengue virus, DENV）与寨卡病毒（Zika virus, ZIKV）均属于黄病毒科（Flaviviridae），主要通过蚊虫叮咬传播。两类病毒在热带及亚热带地区引发的感染病例数持续攀升。登革病毒感染可导致患者出现嗜睡伴严重病症，部分病例可进展为登革休克综合征甚至死亡。目前，寨卡病毒已被证实与吉兰-巴雷综合征（Guillain-Barré syndrome）以及包括小头畸形、发育障碍在内的胎儿畸形（即先天性寨卡综合征）相关。上述两类病毒感染中，免疫应答所发挥的保护与致病作用尚不明确。黏膜相关恒定T细胞（Mucosal-associated invariant T, MAIT）是一类具有强效抗菌活性的先天T细胞群体。此前已有研究推测，MAIT细胞在抗病毒免疫应答中亦可发挥一定作用。本研究针对急性感染期及恢复期登革病毒感染受试者的样本，对MAIT细胞的频率、表型与功能进行了评估。研究发现，在急性登革病毒感染状态下，MAIT细胞共表达活化标志物CD38与HLA-DR的水平显著升高，且在细菌刺激后的γ干扰素（IFNγ）应答能力减弱。此外，本研究还证实MAIT细胞可在体外寨卡病毒感染刺激下产生IFNγ，该应答过程不依赖MR1分子，但依赖IL-12与IL-18。本研究结果提示，MAIT细胞或许在黄病毒科病毒感染的免疫应答中发挥着重要作用。