Mycobacterium tuberculosis, the causative agent of tuberculosis, is the cause of over two million deaths every year. We have previously shown that in mice, Mycobacterium tuberculosis infection induces the production of heme oxygenase, and the subsequent production of carbon monoxide gas is sensed by the bacteria to initiate a dormancy program. Mouse macrophages deficient in heme oxygenase are defective in controlling intracellular Mycobacterium tuberculosis infection and mice deficient in heme oxygenase succumb to disease more readily than wild type mice. While the mechanisms used by mouse macrophages to control intracellular Mycobacterium tuberculosis infection, including nitric oxide synthase, the respiratory burst, acidification and heme oxygenase are well studied; how human macrophages control Mycobacterium tuberculosis infection remains poorly understood. We now show that a polymorphism in the heme oxygenase promoter confers susceptibility to human tuberculosis, that heme oxygenase is induced in human tuberculosis lesions, and that Mycobacterium tuberculosis infection of human macrophages in vitro also induces heme oxygenase. We also show by confocal microscopy that heme oxygenase colocalizes with Mycobacterium tuberculosis in human macrophages, and hee oxygenase enzymatic activity in human macrophages is necessary for inflammatory cytokine production. Thus, we demonstrate an important role for heme oxygenase in controlling Mycobacterium tuberculosis infection.
- Copyright © 2013 by The American Association of Immunologists, Inc.