Abstract
The importance of natural killer (NK) cells in the early immune response to viral or bacterial infection is well known. However, the phenotype, function, and physiologic role of NK cells during the late stage of persistent viral infection have not been extensively studied. Here, we characterized NK cells in mice persistently infected with lymphocytic choriomeningitis virus clone 13 and showed that in contrast to NK cells from acutely infected or uninfected mice, NK cells from chronically infected mice expressed a terminally differentiated phenotype, stronger cytotoxicity, and reduced inhibitory receptor expression. In an in vivo tumor model, chronically infected mice exhibited significantly delayed tumor progression in an NK cell–dependent manner. NK cells from chronically infected mice also expressed high STAT1, and blocking the type I interferon (IFN) receptor revealed that type I IFN signaling directly regulated NK cell cytotoxicity. Our findings indicate that sustained type I IFN signaling during chronic viral infection potentiates the cytolytic function of NK cells and contributes to NK cell–dependent host immune surveillance.
| Original language | English |
|---|---|
| Pages (from-to) | 584-599 |
| Number of pages | 16 |
| Journal | Cancer Immunology Research |
| Volume | 7 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2019 Apr |
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All Science Journal Classification (ASJC) codes
- Immunology
- Cancer Research
Cite this
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Sustained type I interferon reinforces NK cell–mediated cancer immunosurveillance during chronic virus infection. / Oh, Ji Hoon; Kim, Myeong Joon; Choi, Seong Jin; Ban, Young Ho; Lee, Heung Kyu; Shin, Eui Cheol; Lee, Kyung Mi; Ha, Sang Jun.
In: Cancer Immunology Research, Vol. 7, No. 4, 04.2019, p. 584-599.Research output: Contribution to journal › Article
TY - JOUR
T1 - Sustained type I interferon reinforces NK cell–mediated cancer immunosurveillance during chronic virus infection
AU - Oh, Ji Hoon
AU - Kim, Myeong Joon
AU - Choi, Seong Jin
AU - Ban, Young Ho
AU - Lee, Heung Kyu
AU - Shin, Eui Cheol
AU - Lee, Kyung Mi
AU - Ha, Sang Jun
PY - 2019/4
Y1 - 2019/4
N2 - The importance of natural killer (NK) cells in the early immune response to viral or bacterial infection is well known. However, the phenotype, function, and physiologic role of NK cells during the late stage of persistent viral infection have not been extensively studied. Here, we characterized NK cells in mice persistently infected with lymphocytic choriomeningitis virus clone 13 and showed that in contrast to NK cells from acutely infected or uninfected mice, NK cells from chronically infected mice expressed a terminally differentiated phenotype, stronger cytotoxicity, and reduced inhibitory receptor expression. In an in vivo tumor model, chronically infected mice exhibited significantly delayed tumor progression in an NK cell–dependent manner. NK cells from chronically infected mice also expressed high STAT1, and blocking the type I interferon (IFN) receptor revealed that type I IFN signaling directly regulated NK cell cytotoxicity. Our findings indicate that sustained type I IFN signaling during chronic viral infection potentiates the cytolytic function of NK cells and contributes to NK cell–dependent host immune surveillance.
AB - The importance of natural killer (NK) cells in the early immune response to viral or bacterial infection is well known. However, the phenotype, function, and physiologic role of NK cells during the late stage of persistent viral infection have not been extensively studied. Here, we characterized NK cells in mice persistently infected with lymphocytic choriomeningitis virus clone 13 and showed that in contrast to NK cells from acutely infected or uninfected mice, NK cells from chronically infected mice expressed a terminally differentiated phenotype, stronger cytotoxicity, and reduced inhibitory receptor expression. In an in vivo tumor model, chronically infected mice exhibited significantly delayed tumor progression in an NK cell–dependent manner. NK cells from chronically infected mice also expressed high STAT1, and blocking the type I interferon (IFN) receptor revealed that type I IFN signaling directly regulated NK cell cytotoxicity. Our findings indicate that sustained type I IFN signaling during chronic viral infection potentiates the cytolytic function of NK cells and contributes to NK cell–dependent host immune surveillance.
UR - http://www.scopus.com/inward/record.url?scp=85064143675&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85064143675&partnerID=8YFLogxK
U2 - 10.1158/2326-6066.CIR-18-0403
DO - 10.1158/2326-6066.CIR-18-0403
M3 - Article
C2 - 30808680
AN - SCOPUS:85064143675
VL - 7
SP - 584
EP - 599
JO - Cancer immunology research
JF - Cancer immunology research
SN - 2326-6066
IS - 4
ER -