Pivotal role of KARAP/DAP12 adaptor molecule in the natural killer cell-mediated resistance to murine cytomegalovirus infection

The Journal of Experimental Medicine
Hanna SjölinCristina Cerboni

Abstract

Natural killer (NK) cells are major contributors to early defense against infections. Their effector functions are controlled by a balance between activating and inhibiting signals. To date, however, the involvement of NK cell activating receptors and signaling pathways in the defense against pathogens has not been extensively investigated. In mice, several NK cell activating receptors are coexpressed with and function through the immunoreceptor tyrosine-based activation motif (ITAM)-bearing molecule KARAP/DAP12. Here, we have analyzed the role of KARAP/DAP12 in the early antiviral response to murine cytomegalovirus (MCMV). In KARAP/DAP12 mutant mice bearing a nonfunctional ITAM, we found a considerable increase in viral titers in the spleen (30-40-fold) and in the liver (2-5-fold). These effects were attributed to NK cells. The formation of hepatic inflammatory foci appeared similar in wild-type and mutant mice, but the latter more frequently developed severe hepatitis with large areas of focal necrosis. Moreover, the percentage of hepatic NK cells producing interferon gamma was reduced by 56 +/- 22% in the absence of a functional KARAP/DAP12. This is the first study that shows a crucial role for a particular activating signal...Continue Reading

References

May 1, 1990·The Journal of Experimental Medicine·A A ScalzoG R Shellam
Jul 1, 1990·Immunology Today·H G Ljunggren, K Kärre
Jan 1, 1989·Advances in Immunology·G Trinchieri
Jan 1, 1985·The Journal of Experimental Medicine·J F BukowskiR M Welsh
Aug 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·G R ShellamG J Bancroft
Feb 1, 1995·Current Opinion in Immunology·P Scott, G Trinchieri
Jun 1, 1997·Immunology Today·E Vivier, M Daëron
May 2, 1998·Science·H L Ploegh
Jun 8, 1999·Annual Review of Immunology·C A BironT P Salazar-Mather
Feb 5, 2000·Human Immunology·M BléryE Vivier
Apr 5, 2000·The Journal of Clinical Investigation·T P Salazar-MatherC A Biron
Aug 23, 2000·Immunology Today·A Alcami, U H Koszinowski
Oct 25, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·G C PienC A Biron
Mar 29, 2001·Nature Immunology·L L Lanier
Jul 24, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·H AraseL L Lanier
Sep 11, 2001·Nature Immunology·A O DokunW M Yokoyama

❮ Previous
Next ❯

Citations

May 12, 2006·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Karine CrozatBruce Beutler
Oct 1, 2010·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Michal PyzikSilvia M Vidal
Jan 22, 2004·Current Opinion in Immunology·Leonidas N Carayannopoulos, Wayne M Yokoyama
Jun 6, 2003·Current Opinion in Immunology·Lewis L Lanier
Dec 24, 2002·Current Opinion in Immunology·Anthony R French, Wayne M Yokoyama
Dec 31, 2002·Microbes and Infection·Seung Hwan LeeSilvia M Vidal
Dec 31, 2002·Microbes and Infection·Hisashi Arase, Lewis L Lanier
Dec 31, 2002·Microbes and Infection·Wayne M Yokoyama, Anthony A Scalzo
Dec 31, 2002·Microbes and Infection·Scott H Robbins, Laurent Brossay
Jan 16, 2007·Nature Reviews. Immunology·Isaiah R Turnbull, Marco Colonna
Mar 15, 2008·Nature Reviews. Immunology·Lewis L Lanier
Dec 21, 2004·Nature Reviews. Microbiology·Melissa B Lodoen, Lewis L Lanier
Dec 6, 2006·Immunology and Cell Biology·Anthony A ScalzoMariapia A Degli-Esposti
Oct 30, 2003·Viral Immunology·Thais P Salazar-Mather, Kirsten L Hokeness
Jun 29, 2004·Journal of Virology·Ivan BubićUlrich H Koszinowski
Jul 15, 2005·Journal of Virology·Stefan F Wieland, Francis V Chisari
Apr 14, 2006·Journal of Virology·Eva Szomolanyi-TsudaRobert W Finberg
Mar 18, 2005·Annual Review of Immunology·Lewis L Lanier
Oct 24, 2007·Annual Review of Immunology·S M VidalP Gros
Nov 18, 2005·Blood·Sabrina ChiesaElena Tomasello
Oct 8, 2008·BMC Genetics·Abigail R FreemanDaniel G Bradley
Sep 1, 2005·PLoS Genetics·James KelleyJohn Trowsdale
Feb 13, 2008·PLoS Pathogens·Min FangLuis J Sigal
Jun 11, 2011·Journal of Biomedicine & Biotechnology·Michal PyzikSilvia M Vidal
Nov 5, 2014·The Journal of Experimental Medicine·Tsukasa Nabekura, Lewis L Lanier
Feb 25, 2009·Expert Opinion on Therapeutic Targets·Marlowe S TessmerLaurent Brossay
May 1, 2007·Trends in Immunology·Seung-Hwan LeeChristine A Biron
Jul 9, 2004·Scandinavian Journal of Immunology·E BackströmH-G Ljunggren
Feb 28, 2009·European Journal of Immunology·Ilaria TassiMarco Colonna
Nov 15, 2006·Immunological Reviews·Sophie RoetynckSophie Ugolini
Nov 15, 2006·Immunological Reviews·Rayna TakakiLewis L Lanier
Jan 6, 2009·Immunological Reviews·Lewis L Lanier
Jan 18, 2005·Current Opinion in Immunology·Jessica A HamermanLewis L Lanier
Jan 18, 2005·Current Opinion in Immunology·Bruce BeutlerPhilippe Georgel
Dec 8, 2004·Journal of Hepatology·Zhongjun DongZhigang Tian
Nov 28, 2006·Journal of the Neurological Sciences·Ryo KurodaKouichi Mizoguchi
Dec 8, 2005·Immunology Letters·Szabina FodorAttila Mócsai
Oct 29, 2008·Evidence-based Complementary and Alternative Medicine : ECAM·Jia-Ming ChangLe-Mei Hung

❮ Previous
Next ❯

Methods Mentioned

BETA
Assay
PMA
flow cytometry
genetic modifications
genetic modification

Related Concepts

Related Feeds

Cancer Biology: Molecular Imaging

Molecular imaging enables noninvasive imaging of key molecules that are crucial to tumor biology. Discover the latest research in molecular imaging in cancer biology in this feed.