title: NK Cell Responses to Human Tick-Borne Encephalitis Virus Infection.
abstract: Tick-borne encephalitis virus (TBEV) is a flavivirus that is transferred to humans by infected ticks. The virus causes tick-borne encephalitis, a severe infection of the CNS with a high risk for long-lasting sequelae. Currently, no treatment exists for the disease. Understanding the cellular immune response to this infection is important to gain further understanding into the pathogenesis, treatment, and prevention of the disease. NK cells are known to participate in the control of viral infections. We performed a longitudinal analysis of the human NK cell response to TBEV infection in a cohort of infected individuals from the onset of severe clinical symptoms to the convalescence phase. NK cell activation, as measured by expression of Ki67, was apparent at the time of hospitalization. By 3 wk after hospitalization, it decreased to levels seen in healthy controls. Concomitant with the increase in NK cell activation, augmented levels of IL-12, IL-15, IL-18, IFN-γ, and TNF were detected in patient plasma. This TBEV-induced NK cell activation was restricted predominantly to differentiated CD57(+)CD56(dim) NK cells. Functionally, CD56(dim) NK cells responded poorly to target cells at the time of hospitalization, but they recovered functional capacity to control levels during the convalescent phase. In contrast, the responsiveness of NK cells to cytokine stimulation remained intact throughout the disease. These findings demonstrate that NK cells respond to TBEV infection with characteristics that are distinct from those of other human viral infections and provide insights into the NK cell response to clinical TBEV infection.
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 141 86 Stockholm, Sweden;
authors.forename: Kim
authors.initials: K
authors.lastname: Blom
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 141 86 Stockholm, Sweden;
authors.forename: Monika
authors.initials: M
authors.lastname: Braun
authors.affiliation: Department of Infectious Diseases, Lithuanian University of Health Sciences, LT 47116 Kaunas, Lithuania;
authors.forename: Jolita
authors.initials: J
authors.lastname: Pakalniene
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 141 86 Stockholm, Sweden; Department of Viral Immunology, Heinrich-Pette-Institute, Leibniz-Institute for Experimental Virology, 20251 Hamburg, Germany;
authors.forename: Sebastian
authors.initials: S
authors.lastname: Lunemann
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 141 86 Stockholm, Sweden;
authors.forename: Monika
authors.initials: M
authors.lastname: Enqvist
authors.affiliation: Department of Infectious Diseases, Lithuanian University of Health Sciences, LT 47116 Kaunas, Lithuania;
authors.forename: Laura
authors.initials: L
authors.lastname: Dailidyte
authors.affiliation: Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, 141 86 Stockholm, Sweden;
authors.forename: Marie
authors.initials: M
authors.lastname: Schaffer
authors.affiliation: Department of Infectious Diseases, Karolinska University Hospital, 141 86 Stockholm, Sweden; and Unit of Infectious Disease, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 141 86 Stockholm, Sweden.
authors.forename: Lars
authors.identifier: 0000-0002-3530-7382
authors.initials: L
authors.lastname: Lindquist
authors.affiliation: Department of Infectious Diseases, Lithuanian University of Health Sciences, LT 47116 Kaunas, Lithuania; Unit of Infectious Disease, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 141 86 Stockholm, Sweden.
authors.forename: Aukse
authors.initials: A
authors.lastname: Mickiene
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 141 86 Stockholm, Sweden;
authors.forename: Jakob
authors.identifier: 0000-0001-6948-7281
authors.initials: J
authors.lastname: Michaëlsson
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 141 86 Stockholm, Sweden;
authors.forename: Hans-Gustaf
authors.initials: HG
authors.lastname: Ljunggren
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 141 86 Stockholm, Sweden; Department of Infectious Diseases, Karolinska University Hospital, 141 86 Stockholm, Sweden; and sara.gredmark.russ@ki.se.
authors.forename: Sara
authors.initials: S
authors.lastname: Gredmark-Russ
mesh_terms: D004669:Encephalitis Viruses, Tick-Borne / Q000276:immunology; D004675:Encephalitis, Tick-Borne / Q000276:immunology* / Q000821:virology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*