NK cells are activated and primed for skin-homing during acute dengue virus infection in humans

Christine L. Zimmer, Martin Cornillet, Carles Solà-Riera, Ka Wai Cheung, Martin A. Ivarsson, Mei Qiu Lim, Nicole Marquardt, Yee Sin Leo, David Chien Lye, Jonas Klingström, Paul A. MacAry, Hans Gustaf Ljunggren, Laura Rivino, Niklas K. Björkström*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

34 Citations (Scopus)
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Despite animal models showing that natural killer (NK) cells are important players in the early defense against many viral infections, the NK cell response is poorly understood in humans. Here we analyze the phenotype, temporal dynamics, regulation and trafficking of NK cells in a patient cohort with acute dengue virus infection. NK cells are robustly activated and proliferate during the first week after symptom debut. Increased IL-18 levels in plasma and in induced skin blisters of DENV-infected patients, as well as concomitant signaling downstream of the IL-18R, suggests an IL-18-dependent mechanism in driving the proliferative NK cell response. Responding NK cells have a less mature phenotype and a distinct chemokine-receptor imprint indicative of skin-homing. A corresponding NK cell subset can be localized to skin early during acute infection. These data provide evidence of an IL-18-driven NK cell proliferation and priming for skin-homing during an acute viral infection in humans.

Original languageEnglish
Article number3897 (2019)
Number of pages15
JournalNature Communications
Publication statusPublished - 29 Aug 2019


  • Innate lymphoid cells
  • Interleukins
  • Signal transduction
  • Viral infection


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