Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
PARP-1 controls NK cell recruitment to the site of viral infection
Qiyang Shou, … , Xiaopei Huang, Yiping Yang
Qiyang Shou, … , Xiaopei Huang, Yiping Yang
Published June 20, 2019
Citation Information: JCI Insight. 2019;4(12):e121291. https://doi.org/10.1172/jci.insight.121291.
View: Text | PDF
Research Article Immunology Virology

PARP-1 controls NK cell recruitment to the site of viral infection

  • Text
  • PDF
Abstract

The activation and recruitment of NK cells to the site of viral infection are crucial for virus control. However, it remains largely unknown what controls the recruitment of the activated NK cells to the infection site. In a model of intraperitoneal infection with vaccinia virus (VV), we showed that poly(ADP-ribose) polymerase-1 (PARP-1), a sensor of DNA damage, is critical for NK cell recruitment to the site of infection and viral control in vivo. We further demonstrated that PARP-1 promotes the production of CCL2 and that the CCL2-CCR2 axis is essential for NK cell recruitment to the infection site. In addition, we demonstrated that peritoneal macrophages are the main producer of PARP-1–dependent CCL2 secretion. Mechanistically, PARP-1 functions as a regulator of NF-κB by promoting its nuclear translocation and binding to its response sequences in macrophages upon VV infection. Taken together, our results reveal a potentially previously unknown role for PARP-1–dependent CCL2 production in NK cell migration and viral control and may provide important insights into the design of effective NK cell–based therapies for viral infections and cancer.

Authors

Qiyang Shou, Huiying Fu, Xiaopei Huang, Yiping Yang

×

Figure 1

Inhibition of PARP-1 activity suppresses NK cell migration in response to intraperitoneal VV infection and delays viral clearance.

Options: View larger image (or click on image) Download as PowerPoint
Inhibition of PARP-1 activity suppresses NK cell migration in response t...
C57BL/6 mice were either treated with PARP-1 inhibitor AG14361 (10 mg/kg, i.v.) (VV+AG14361) or PBS (VV) and subjected to infection with VV (5 × 106 PFU, i.p.). Naive mice were used as controls. Three days later, peritoneal fluid was harvested and assayed for DX5+CD3– NK cells by flow cytometry. (A) FACS plots showing percentages of DX5+CD3– NK cells in the peritoneal fluids. (B) The mean absolute NK cell numbers ± SD are shown (n = 3). (C) IFN-γ production was measured intracellularly and the mean percentages of IFN-γ+ NK cells are shown (n = 3). (D) The viral titer in peritoneal fluid was measured by the standard plaque assay and the mean viral titers ± SD are shown (n = 4). **P < 0.01, 2-tailed Student’s t test.

Copyright © 2022 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts