title: The quantity of nitric oxide released by macrophages regulates Chlamydia-induced disease.
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.
authors.affiliation: Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Huang
authors.forename: Fred J
authors.initials: FJ
authors.lastname: DeGraves
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Lenz
authors.forename: Dongya
authors.initials: D
authors.lastname: Gao
authors.forename: Pu
authors.initials: P
authors.lastname: Feng
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Tobias
authors.initials: T
authors.lastname: Schlapp
authors.forename: Bernhard
authors.initials: B
authors.lastname: Kaltenboeck
mesh_terms: D000818:Animals; D001119:Arginase / Q000235:genetics / Q000378:metabolism; D001120:Arginine / Q000378:metabolism; D002384:Catalysis; D002689:Chlamydia / Q000502:physiology*; D002690:Chlamydia Infections / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D008264:Macrophages / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D001119:Arginase