The Quantity of Nitric Oxide Released by Macrophages Regulates Chlamydia-induced Disease

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2002 Mar 21

PMID 11904441

Citations 22

Authors

Jin Huang

Fred J DeGraves

Stephen D Lenz

Dongya Gao

Pu Feng

Dan Li

Tobias Schlapp

Bernhard Kaltenboeck

Affiliations

Soon will be listed here.

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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