Huang Jin, DeGraves Fred J, Lenz Stephen D, Gao Dongya, Feng Pu, Li Dan, Schlapp Tobias, Kaltenboeck Bernhard
Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA.
Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3914-9. doi: 10.1073/pnas.062578399.
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.
衣原体属的细胞内细菌会引发众多典型的慢性疾病，常常伴有使人虚弱的后遗症。感染衣原体细菌后疾病易感性的遗传决定因素尚不清楚。中度呼吸道感染后，C57BL/6小鼠会患上严重肺炎且对衣原体的免疫力较差，而BALB/c小鼠则不会患病，并产生强烈的Th1免疫反应。我们在此表明，受感染的C57BL/6巨噬细胞比BALB/c巨噬细胞释放更多由一氧化氮合酶2（NOS2）合成的一氧化氮（NO），并且其精氨酸酶II的mRNA浓度较低，精氨酸酶II是NOS2对共同底物L-精氨酸的竞争物。通过不完全抑制NOS2来减少而非消除NO的产生，可消除C57BL/6小鼠对衣原体诱导疾病的易感性。因此，受感染巨噬细胞释放的NO量是调节对衣原体感染的致病和保护反应的效应机制，而控制NO产生的基因决定了对衣原体疾病的易感性。
