Bacillus Calmette Guerin triggers the IL-12/IFN-gamma axis by an IRAK-4- and NEMO-dependent, non-cognate interaction between monocytes, NK, and T lymphocytes

European Journal of Immunology
Jacqueline FeinbergJean-Laurent Casanova

Abstract

The IL-12/IFN-gamma axis is crucial for protective immunity to Mycobacterium in humans and mice. Our goal was to analyze the relative contribution of various human blood cell subsets and molecules to the production of, or response to IL-12 and IFN-gamma. We designed an assay for the stimulation of whole blood by live M. bovis Bacillus Calmette-Guerin (BCG) alone, or BCG plus IL-12 or IFN-gamma, measuring IFN-gamma and IL-12 levels. We studied patients with a variety of specific inherited immunodeficiencies resulting in a lack of leukocytes, or T, B, and/or NK lymphocytes, or polymorphonuclear cells, or a lack of expression of key molecules such as HLA class II, CD40L, NF-kappaB essential modulator (NEMO), and IL-1 receptor-associated kinase-4 (IRAK-4). Patients with deficiencies in IL-12p40, IL-12 receptor beta1 chain (IL-12Rbeta1), IFN-gammaR1, IFN-gammaR2, and STAT-1 were used as internal controls. We showed that monocytes were probably the main producers of IL-12, and that NK and T cells produced similar amounts of IFN-gamma. NEMO and IRAK-4 were found to be important for IL-12 production and subsequent IFN-gamma production, while a lack of CD40L or HLA class II had no major impact on the IL-12/IFN-gamma axis. The stimulatio...Continue Reading

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Citations

Jul 16, 2008·The Journal of Experimental Medicine·Guillaume VogtJean-Laurent Casanova
Jul 6, 2011·The Journal of Experimental Medicine·Luyan LiuJean-Laurent Casanova
Mar 1, 2005·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Namik OzbekJean-Laurent Casanova
Jan 27, 2011·Human Molecular Genetics·Ithaisa SologurenCarlos Rodríguez-Gallego
Dec 18, 2004·Current Opinion in Hematology·Tatiana LawrenceJean-Laurent Casanova
May 20, 2009·The Pediatric Infectious Disease Journal·Petra MoilanenUlla M Saarinen-Pihkala
Nov 9, 2010·Medicine·Ludovic de BeaucoudreyJean-Laurent Casanova
Feb 13, 2007·Journal of Medical Genetics·Jacinta BustamanteJean-Laurent Casanova
May 12, 2007·Annual Review of Genomics and Human Genetics·A FortinP Gros
May 14, 2009·The Journal of Clinical Investigation·Ariane ChapgierJean-Laurent Casanova
Aug 29, 2006·PLoS Genetics·Ariane ChapgierJean-Laurent Casanova
May 14, 2014·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Laurent AbelErwin Schurr
Jan 4, 2008·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Heidi GlosliTore G Abrahamsen
Aug 11, 2005·European Journal of Pediatrics·Davood MansouriJean-Laurent Casanova
Dec 21, 2006·The Journal of Experimental Medicine·Michishige HaradaMasaru Taniguchi
Mar 1, 2012·Indian Journal of Pediatrics·Sheela NampoothiriJean-Laurent Casanova
Dec 17, 2008·The Journal of Allergy and Clinical Immunology·Saleh Al-Muhsen, Jean-Laurent Casanova
Aug 26, 2015·The Journal of Experimental Medicine·Alexandra Y KreinsStéphanie Boisson-Dupuis
May 24, 2014·International Journal of Obesity : Journal of the International Association for the Study of Obesity·C-L YenC-C Shieh
Aug 2, 2016·Chemotherapy Research and Practice·Taj Ali KhanMuhammad Nasser Abbas
Nov 5, 2016·The Journal of Experimental Medicine·Yi WangJean-Laurent Casanova
Sep 19, 2009·International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases·Patricia Méndez-Samperio
Sep 26, 2006·Seminars in Immunology·Orchidée Filipe-SantosJean-Laurent Casanova
Mar 6, 2018·Critical Reviews in Clinical Laboratory Sciences·Ana Esteve-SoléJacinta Bustamante
Dec 20, 2017·Immunogenetics·Maryam Alinejad DizajAliakbar Velayati
Jun 1, 2005·Nature Genetics·Guillaume VogtJean-Laurent Casanova
Jul 12, 2018·Journal of Clinical Immunology·Jérémie RosainJacinta Bustamante
Sep 14, 2018·Journal of Leukocyte Biology·Rym OuniChaouki Benabdessalem
Feb 27, 2010·American Journal of Medical Genetics. Part a·Carolina PrandoJean-Laurent Casanova

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