IL-22 hinders antiviral T cell responses and exacerbates ZIKV encephalitis in immunocompetent neonatal mice

Yuejin Liang, Panpan Yi, Wenjuan Ru, Zuliang Jie, Hui Wang, Tamer Ghanayem, Xiaofang Wang, Edrous Alamer, Jinjun Liu, Haitao Hu, Lynn Soong, Jiyang Cai, Jiaren Sun

Research output: Contribution to journalArticle

Abstract

Background: The Zika virus (ZIKV) outbreak that occurred in multiple countries was linked to increased risk of nervous system injuries and congenital defects. However, host immunity- and immune-mediated pathogenesis in ZIKV infection are not well understood. Interleukin-22 (IL-22) is a crucial cytokine for regulating host immunity in infectious diseases. Whether IL-22 plays, a role in ZIKV infection is unknown. Methods: The cellular source of IL-22 was identified in IFNAR -/- mice and wild-type (WT) neonatal mice during ZIKV infection. To determine the role of IL-22, we challenged 1-day-old WT and IL-22 -/- mice with ZIKV and monitored clinical manifestations. Glial cell activation in the brain was assessed by confocal imaging. ZIKV-specific CD8+ T cell responses in both the spleen and brain were analyzed by flow cytometry. In addition, glial cells were cultured in vitro and infected with ZIKV in the presence of IL-22, followed by the evaluation of cell proliferation, cytokine expression, and viral loads. Results: We found that γδT cells were the main source of IL-22 during ZIKV infection in both the spleen and brain. WT mice began to exhibit weight loss, staggered steps, bilateral hind limb paralysis, and weakness at 10 days post-infection (dpi) and ultimately succumbed to infection at 16-19 dpi. IL-22 deficiency lessened weight loss, moderated the systemic inflammatory response, and greatly improved clinical signs of neurological disease and mortality. ZIKV infection also induced the activation of microglia and astrocytes in vitro. Additional analysis demonstrated that the absence of IL-22 resulted in reduced activation of microglia and astrocytes in the cortex. Although IL-22 displayed a negligible effect on glial cells in vitro, IL-22 -/- mice mounted more vigorous ZIKV-specific CD8+ T cell responses, which led to a more effective control of ZIKV in the brain. Conclusions: Our data revealed a pathogenic role of IL-22 in ZIKV encephalitis.

Original languageEnglish (US)
Article number249
JournalJournal of neuroinflammation
Volume17
Issue number1
DOIs
StatePublished - Aug 25 2020

Keywords

  • Astrocytes
  • Brain
  • CD8
  • Encephalitis
  • IL-22
  • Microglia
  • Neonatal mice
  • ZIKV

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology
  • Neurology
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'IL-22 hinders antiviral T cell responses and exacerbates ZIKV encephalitis in immunocompetent neonatal mice'. Together they form a unique fingerprint.

  • Cite this