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PARP-1 controls NK cell recruitment to the site of viral infection
- Source :
- JCI Insight. 4
- Publication Year :
- 2019
- Publisher :
- American Society for Clinical Investigation, 2019.
-
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.
- Subjects :
- 0301 basic medicine
DNA damage
Poly ADP ribose polymerase
Cell
Poly (ADP-Ribose) Polymerase-1
Biology
CCL2
Peritoneal Diseases
Virus
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Vaccinia
medicine
Animals
Secretion
Chemokine CCL2
NF-kappa B
Cell migration
General Medicine
Killer Cells, Natural
Mice, Inbred C57BL
030104 developmental biology
medicine.anatomical_structure
chemistry
030220 oncology & carcinogenesis
Immunology
Macrophages, Peritoneal
DNA Damage
Research Article
Subjects
Details
- ISSN :
- 23793708
- Volume :
- 4
- Database :
- OpenAIRE
- Journal :
- JCI Insight
- Accession number :
- edsair.doi.dedup.....3dcd7d270e9099b865a518e179c1fccc