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 and Niklas K. Björkström ()
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Christine L. Zimmer: Karolinska University Hospital
Martin Cornillet: Karolinska University Hospital
Carles Solà-Riera: Karolinska University Hospital
Ka-Wai Cheung: DUKE-NUS Medical School
Martin A. Ivarsson: Karolinska University Hospital
Mei Qiu Lim: DUKE-NUS Medical School
Nicole Marquardt: Karolinska University Hospital
Yee-Sin Leo: Tan Tock Seng Hospital
David Chien Lye: Tan Tock Seng Hospital
Jonas Klingström: Karolinska University Hospital
Paul A. MacAry: National University of Singapore
Hans-Gustaf Ljunggren: Karolinska University Hospital
Laura Rivino: DUKE-NUS Medical School
Niklas K. Björkström: Karolinska University Hospital

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-11878-3

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