Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Apr;153(4):455-465.
doi: 10.1111/imm.12858. Epub 2017 Dec 11.

Differences in activation and tissue homing markers of natural killer cell subsets during acute dengue infection

Rassamon Keawvichit  1   2 , Ladawan Khowawisetsut  3 , Sakaorat Lertjuthaporn  1   2 , Kanchana Tangnararatchakit  4 , Nopporn Apiwattanakul  4 , Sutee Yoksan  5 , Ampaiwan Chuansumrit  4 , Kulkanya Chokephaibulkit  6 , Aftab A Ansari  7 , Nattawat Onlamoon  1 , Kovit Pattanapanyasat  1
Affiliations

Differences in activation and tissue homing markers of natural killer cell subsets during acute dengue infection

Rassamon Keawvichit et al. Immunology. 2018 Apr.

Abstract

Dengue virus (DENV) infection is considered one of the most important mosquito-borne diseases. It causes a spectrum of illness that could be due to qualitative and/or quantitative difference(s) of the natural killer (NK) cell responses during acute DENV infection. This view prompted us to perform a detailed phenotypic comparative characterization of NK cell subsets from DENV-infected patients with dengue fever (DF), patients with dengue haemorrhagic fever (DHF) and healthy controls. The activation/differentiation molecules, CD69 and CD57 and a variety of tissue homing molecules were analysed on the CD56hi CD16- and CD56lo CD16+ NK cells. Although there was no increase in the frequency of the total NK cells during DENV infection compared with the healthy individuals, there was a significant increase in the frequency of the CD56hi CD16- subset and the frequency of CD69 expression by both NK cell subsets during the febrile phase of infection. We also found an increase in the frequencies of cells expressing CD69 and CD57 in the CD56lo CD16+ subset compared with those in the CD56hi CD16- subset. Moreover, although the CD56lo CD16+ subset contained a high frequency of cells expressing skin-homing markers, the CD56hi CD16- subset contained a high frequency of cells expressing bone marrow and lymph node trafficking markers. Interestingly, no differences of these NK cell subsets were noted in samples from patients with DF versus those with DHF. These findings suggest that activation and differentiation and the patterns of tissue homing molecules of the two major NK cell subsets are different and that these might play a critical role in the immune response against acute DENV infection.

Keywords: cell trafficking; dengue infection; innate immunity; natural killer cells.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Gating strategy used for the natural killer (NK) cells in peripheral blood. Dot plots show the two major populations of the NK cell subsets, which are CD56hi CD16− and CD56lo CD16+ NK cells on the gated population of CD14−/CD3−/CD19−/HLA− DR−/CD7+ cells.
Figure 2
Figure 2
Comparison of the frequencies of natural killer (NK) cells. Bar graphs demonstrating the frequency of total NK cells (a), and the frequency of the CD56hi CD16− NK cell subset (b) and CD56lo CD16+ NK cell subset (c) in total NK cell population in samples from healthy controls (n = 15), dengue fever (DF) patients (n = 14) and dengue haemorrhagic fever (DHF) patients (n = 22). Although there were no significant changes in the frequencies of total NK cells during dengue virus (DENV) infection, the frequencies of CD56hi CD16− NK cells from DF and DHF patients were significantly increased (P < 0·05 and P = 0·02, respectively), and the frequencies of CD56lo CD16+ NK cells in DENV‐infected patients was decreased, especially in DF patients (P = 0·04). (*P < 0·05, Mann–Whitney U‐test).
Figure 3
Figure 3
CD69 and CD57 expression on natural killer (NK) cell subsets in samples from patients with different dengue virus (DENV) severity. Bar graphs show the frequency of CD69+ CD56hi CD16− NK cells (a) CD69+ CD56lo CD16+ NK cells (b) CD57+ CD56hi CD16− NK cells and (c) CD57+ CD56lo CD16+ NK cells (d) in samples from healthy individuals (n = 15), dengue fever (DF) patients (n = 14) and dengue haemorrhagic fever (DHF) patients (n = 22). (*P < 0·05, Mann–Whitney U‐test).
Figure 4
Figure 4
Kinetics of natural killer (NK) cell activation and differentiation during acute dengue virus (DENV) infection. Bar graphs show the frequency of CD69‐expressing CD56hi CD16− NK cells (a) and CD56lo CD16+ NK cells (b), and the percentage of CD56hi CD16− NK cells (c) and CD56lo CD16+ NK cells (d) that express CD57 in samples from day −3 (D−3) to day +3 (D+3) during DENV infection.
Figure 5
Figure 5
Expression of homing molecules on activated natural killer (NK) cell subsets in dengue virus (DENV) ‐infected patients. Bar graphs show the frequency of homing markers expressed by activated CD56hi CD16− NK cells (a) and CD56lo CD16+ NK cells (b) in samples from DENV‐infected patients (D) and healthy individuals (H). (*P < 0·05, Mann–Whitney U‐test).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL et al The global distribution and burden of dengue. Nature 2013; 496:504–7. - PMC - PubMed
    1. Centers for Disease Control and Prevention . Dengue 2009 [WWW document]. URL http://www.cdc.gov/dengue/clinicallab/clinical.html [accessed 6 September 2014].
    1. Ligon BL. Dengue fever and dengue hemorrhagic fever: a review of the history, transmission, treatment, and prevention. Semin Pediatr Infect Dis 2005; 16:60–5. - PubMed
    1. Nielsen DG. The relationship of interacting immunological components in dengue pathogenesis. Virol J 2009; 6:211. - PMC - PubMed
    1. Whitehorn J, Simmons CP. The pathogenesis of dengue. Vaccine 2011; 29:7221–8. - PubMed

Publication types