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J Immunol. 2016 Jan 15;196(2):547-52. doi: 10.4049/jimmunol.1501415. Epub 2015 Dec 18.

Cutting Edge: Novel Tmem173 Allele Reveals Importance of STING N Terminus in Trafficking and Type I IFN Production.

Author information

1
Program in Immunology, Tufts University, Boston, MA 02111;
2
Program in Innate Immunity, Division of Infectious Diseases, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605;
3
Petrozavodsk State University, Petrozavodsk, Republic of Karelia, Russia 185910;
4
Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, Boston, MA 02111; and.
5
Program in Immunology, Tufts University, Boston, MA 02111; Petrozavodsk State University, Petrozavodsk, Republic of Karelia, Russia 185910; Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, Boston, MA 02111; and Graduate Program in Genetics, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111 Alexander.Poltorak@tufts.edu.

Abstract

With the stimulator of IFN genes (STING) C terminus being extensively studied, the role of the N-terminal domain (NTD) of STING remains an important subject of investigation. In this article, we identify novel mutations in NTD of Sting of the MOLF strain in response to HSV and Listeria monocytogenes both in vitro and in vivo. These mutations are responsible for low levels of IFN-β caused by failure of MOLF STING to translocate from the endoplasmic reticulum. These data provide evidence that the NTD of STING affects DNA responses via control of trafficking. They also show that the genetic diversity of wild-derived mice resembles the diversity observed in humans. Several human alleles of STING confer attenuated IFN-I production similar to what we observe with the MOLF Sting allele, a crucial functional difference not apparent in classical inbred mice. Thus, understanding the functional significance of polymorphisms in MOLF STING can provide basic mechanistic insights relevant to humans.

PMID:
26685207
PMCID:
PMC4707084
DOI:
10.4049/jimmunol.1501415
[Indexed for MEDLINE]
Free PMC Article

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