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

## TL;DR

This study tracks immune responses in people with mild Zika virus infection and finds that Th17 immune activity is linked to both strong antibody responses and longer neurological symptoms.

## Contribution

The study provides new insights into the longitudinal immune response to mild Zika virus infection and the dual role of Th17 polarization.

## Key findings

- Early antiviral response is dominated by IFN-γ and TNF-α, regulated by IL-10.
- Th1 and Th17 cytokines peak and persist for up to one month after symptom onset.
- Early Th17 cytokines correlate with stronger antibody responses and longer neurological symptoms.

## Abstract

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.