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.

Details

Title
NK cells are activated and primed for skin-homing during acute dengue virus infection in humans
Author
Zimmer, Christine L 1 ; Cornillet, Martin 1 ; Solà-Riera, Carles 1 ; Ka-Wai Cheung 2 ; Ivarsson, Martin A 1 ; Mei Qiu Lim 2 ; Marquardt, Nicole 1   VIAFID ORCID Logo  ; Yee-Sin, Leo 3 ; David Chien Lye 4   VIAFID ORCID Logo  ; Klingström, Jonas 1   VIAFID ORCID Logo  ; MacAry, Paul A 5 ; Ljunggren, Hans-Gustaf 1 ; Rivino, Laura 6 ; Björkström, Niklas K 1   VIAFID ORCID Logo 

1  Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden 
2  Programme in Emerging Infectious Diseases, DUKE-NUS Medical School, Singapore, Singapore 
3  Institute of Infectious Diseases and Epidemiology, Communicable Disease Centre, Tan Tock Seng Hospital, Singapore, Singapore; Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore 
4  Institute of Infectious Diseases and Epidemiology, Communicable Disease Centre, Tan Tock Seng Hospital, Singapore, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore 
5  Immunology Programme, Life Science Institute and Department of Microbiology and Immunology, National University of Singapore, Singapore, Singapore 
6  Programme in Emerging Infectious Diseases, DUKE-NUS Medical School, Singapore, Singapore; School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK 
Pages
1-15
Publication year
2019
Publication date
Aug 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-019-11878-3
ProQuest document ID
2282428368
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.