Increased level and interferon-γ production of circulating natural killer cells in patients with scrub typhus

PLoS Negl Trop Dis. 2017 Jul 27;11(7):e0005815. doi: 10.1371/journal.pntd.0005815. eCollection 2017 Jul.

Abstract

Background: Natural killer (NK) cells are essential immune cells against several pathogens. Not much is known regarding the roll of NK cells in Orientia tsutsugamushi infection. Thus, this study aims to determine the level, function, and clinical relevance of NK cells in patients with scrub typhus.

Methodology/principal findings: This study enrolled fifty-six scrub typhus patients and 56 health controls (HCs). The patients were divided into subgroups according to their disease severity. A flow cytometry measured NK cell level and function in peripheral blood. Circulating NK cell levels and CD69 expressions were significantly increased in scrub typhus patients. Increased NK cell levels reflected disease severity. In scrub typhus patients, tests showed their NK cells produced higher amounts of interferon (IFN)-γ after stimulation with interleukin (IL)-12 and IL-18 relative to those of HCs. Meanwhile, between scrub typhus patients and HCs, the cytotoxicity and degranulation of NK cells against K562 were comparable. CD69 expressions were recovered to the normal levels in the remission phase.

Conclusions: This study shows that circulating NK cells are activated and numerically increased, and they produced more IFN-γ in scrub typhus patients.

MeSH terms

  • Aged
  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • Case-Control Studies
  • Female
  • Flow Cytometry
  • Humans
  • Interferon-gamma / immunology*
  • Interleukin-12 / pharmacology
  • Interleukin-18 / pharmacology
  • Killer Cells, Natural / immunology*
  • Lectins, C-Type / metabolism
  • Leukocyte Count
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Orientia tsutsugamushi
  • Scrub Typhus / immunology*
  • Severity of Illness Index

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • Interleukin-18
  • Lectins, C-Type
  • Interleukin-12
  • Interferon-gamma

Grants and funding

This work was supported by the National Research Foundation of Korea funded by the Korean Government (Grants 2013R1A2A2A01067956[YWP], 2015R1D1A1A01059762[SJKe], 2015R1D1A4A01019017[YNC], 2016R1A6A3A11930514[HMJ] and 2017R1C1B1008164[SJKa]), the Chonnam National University Hospital Biomedical Research Institute (Grants CRI13032-1[SJKa], CRI13905-22.5[YWP] and CRI17034-21[SJKe]), and the Korea Health Technology R&D Project (Grant HI17C0947[YWP]). The funders had no role in study design, data collection and analysis, decision to publish of the manuscript.