The quantity of nitric oxide released by macrophages regulates Chlamydia-induced disease

Proceedings of the National Academy of Sciences of the United States of America
Jin HuangBernhard Kaltenboeck

Abstract

Intracellular bacteria of the genus Chlamydia cause numerous typically chronic diseases, frequently with debilitating sequelae. Genetic determinants of disease susceptibility after infection with Chlamydia bacteria are unknown. C57BL/6 mice develop severe pneumonia and poor immunity against Chlamydia after moderate respiratory infection whereas BALB/c mice are protected from disease and develop vigorous Th1 immunity. Here we show that infected C57BL/6 macrophages release more NO synthesized by NO synthase 2 (NOS2) than BALB/c macrophages and have lower mRNA concentrations of arginase II, a competitor of NOS2 for the common substrate, l-arginine. Reduction, but not elimination, of NO production by incomplete inhibition of NOS2 abolishes susceptibility of C57BL/6 mice to Chlamydia-induced disease. Thus, the quantity of NO released by infected macrophages is the effector mechanism that regulates between pathogenic and protective responses to chlamydial infection, and genes controlling NO production determine susceptibility to chlamydial disease.

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Citations

Mar 9, 2004·Vaccine·Vittorio SambriRoberto Cevenini
Sep 21, 2004·Nature Reviews. Microbiology·Ferric C Fang
Aug 30, 2008·Infection and Immunity·Chengming WangBernhard Kaltenboeck
Jul 24, 2004·Infection and Immunity·Malgosia K Matyszak, J S Hill Gaston
Aug 19, 2007·Journal of Bacteriology·Teresa N Giles, David E Graham
Dec 8, 2004·Journal of Clinical Microbiology·JunBae JeeBernhard Kaltenboeck
May 4, 2011·World Journal of Diabetes·Cheng-Ming Wang, Bernhard Kaltenboeck
Oct 29, 2010·The Veterinary Journal·Petra ReinholdBernhard Kaltenboeck
Apr 7, 2005·Vaccine·Katherine Stemke-HaleStephen Albert Johnston
Apr 14, 2005·Microbes and Infection·Gilbert GreubJean-Louis Mege
Jan 23, 2009·FEMS Immunology and Medical Microbiology·Mirja Puolakkainen
Feb 8, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nuruddeen D LewisKeith T Wilson
Jul 22, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Alain P GobertKeith T Wilson
May 7, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sébastien DuleuAlain P Gobert
Apr 20, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Luis E PerezPeter C Melby
Nov 25, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kemin ChenHelen Braley-Mullen
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Apr 25, 2019·Amino Acids·Yvonne L LatourKeith T Wilson
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