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

First Author  Shou Q Year  2019
Journal  JCI Insight Volume  4
Issue  12 PubMed ID  31217354
Mgi Jnum  J:294576 Mgi Id  MGI:6455334
Doi  10.1172/jci.insight.121291 Citation  Shou Q, et al. (2019) PARP-1 controls NK cell recruitment to the site of viral infection. JCI Insight 4(12)
abstractText  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-kappaB 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.
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