The quantity of nitric oxide released by macrophages regulates Chlamydia-induced disease.
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.
Huang
Jin
J
Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA.
DeGraves
Fred J
FJ
Lenz
Stephen D
SD
Gao
Dongya
D
Feng
Pu
P
Li
Dan
D
Schlapp
Tobias
T
Kaltenboeck
Bernhard
B
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
D012333:RNA, Messenger; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D001119:Arginase