Longitudinal Monitoring of Systemic Cytokines After Mild Zika Virus Infection Revealed an Association Between Th17 Polarization and Clinical and Serological Outcomes

Zika virus (ZIKV) is a neurotropic virus that can cause a variety of neurological manifestations, ranging from mild forms to severe disorders like Guillain-Barré syndrome and congenital Zika syndrome. The pathophysiology of these complications is not fully understood, but they have been linked to host immune responses, particularly a proinflammatory Th1/Th17 profile. In this study, the kinetics of 14 cytokines were characterized in ZIKV-infected patients recruited in French Guiana in 2016-2017. Cytokine concentrations were quantified using a multiplexed bead-based immunoassay in serum samples collected sequentially from 36 patients during the first month after symptom onset. This longitudinal follow-up provides chronological information on the immune response to mild-to-moderate ZIKV infection, with an early antiviral response dominated by IFN-γ, TNF-α and regulated by IL-10, followed by a peak of Th1 and then Th17-associated cytokines that persists for up to 1 month. The early presence of IL-17A, IL-21, and IL-23 was positively correlated with the maximum amplitude of the serological response (total anti-ZIKV IgG and seroneutralization titers), but also with the duration of neurological symptoms (paresthesia and muscle strength decrease), highlighting the bivalent role of Th17 immune response in ZIKV pathogenesis.