Journal
JOURNAL OF IMMUNOLOGY
Volume 196, Issue 11, Pages 4641-4649Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1500434
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Funding
- National Institutes of Health [RO1 AI099439, R21 AI111023, U19 AI109725, T32 AI5284, T32 AI7520, R01 DK099478, R01 DA09238]
- National Institutes of Health (National Institute of Allergy and Infectious Diseases) [N01-AO02738]
- Disease Oriented Clinical Scholars Program at University of Texas Southwestern
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Mycobacterium tuberculosis, the causative agent of tuberculosis, is responsible for 1.5 million deaths annually. We previously showed that M. tuberculosis infection in mice induces expression of the CO-producing enzyme heme oxygenase (HO1) and that CO is sensed by M. tuberculosis to initiate a dormancy program. Further, mice deficient in HO1 succumb to M. tuberculosis infection more readily than do wild-type mice. Although mouse macrophages control intracellular M. tuberculosis infection through several mechanisms, such as NO synthase, the respiratory burst, acidification, and autophagy, how human macrophages control M. tuberculosis infection remains less well understood. In this article, we show that M. tuberculosis induces and colocalizes with HO1 in both mouse and human tuberculosis lesions in vivo, and that M. tuberculosis induces and colocalizes with HO1 during primary human macrophage infection in vitro. Surprisingly, we find that chemical inhibition of HO1 both reduces inflammatory cytokine production by human macrophages and restricts intracellular growth of mycobacteria. Thus, induction of HO1 by M. tuberculosis infection may be a mycobacterial virulence mechanism to enhance inflammation and bacterial growth.
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