IgA-driven neutrophil activation underlies post-Zika severe dengue disease in humans.

ABSTRACT: The four dengue virus serotypes (DENV1-4) and the related Zika flavivirus (ZIKV) are major public health concerns worldwide. Primary immunity against ZIKV increases the risk of a subsequent severe DENV2 infection, presenting a significant challenge for developing safe and effective ZIKV vaccines. However, the mechanisms driving this phenomenon remain unclear. Leveraging our long-standing Pediatric Dengue Cohort Study in Nicaragua, we show that serum anti-NS1 IgA antibodies elicited after a primary ZIKV infection drive neutrophil activation and correlate with increased risk of subsequent severe DENV2 disease. Depletion experiments combined with ex vivo functional NETosis assays confirmed that anti-NS1 IgA antibodies drive neutrophil activation in dengue hemorrhagic fever/dengue shock

SUBMITTER: Cardona-Ospina JA 

PROVIDER: S-EPMC11952487 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature