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PMID: 18474359 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Mycobacterium tuberculosis senses host-derived carbon monoxide during macrophage infection.

Cell host & microbe ·Vol. 3 ·No. 5 ·2008-05-15 ·Pages 323-30

Shiloh MU, Manzanillo P, Cox JS

Abstract

Mycobacterium tuberculosis (MTB) expresses a set of genes known as the dormancy regulon in vivo. These genes are expressed in vitro in response to nitric oxide (NO) or hypoxia, conditions used to model MTB persistence in latent infection. Although NO, a macrophage product that inhibits respiration, and hypoxia are likely triggers in vivo, additional cues could activate the dormancy regulon during infection. Here, we show that MTB infection stimulates expression of heme oxygenase (HO-1) by macrophages and that the gaseous product of this enzyme, carbon monoxide (CO), activates expression of the dormancy regulon. Deletion of macrophage HO-1 reduced expression of the dormancy regulon. Furthermore, we show that the MTB DosS/DosT/DosR two-component sensory relay system is required for the response to CO. Together, these findings demonstrate that MTB senses CO during macrophage infection. CO may represent a general cue used by pathogens to sense and adapt to the host environment.

MeSH Terms
Animals Carbon Monoxide/immunology Cells, Cultured Gene Expression Regulation, Bacterial Heme Oxygenase-1/genetics,immunology Macrophages/enzymology,immunology,microbiology Mice Mice, Inbred BALB C Mycobacterium tuberculosis/genetics,immunology Regulon Tuberculosis/microbiology
Chemicals
Carbon Monoxide HMOX1 protein, human Heme Oxygenase-1
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Shiloh Michael U
Department of Medicine, Division of Infectious Diseases, University of California, San Francisco, San Francisco, CA 94158, USA.
Manzanillo Paolo
Cox Jeffery S
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Article Info
Journal
Cell host & microbe
Abbr.
Cell Host Microbe
ISSN
1934-6069
DOI
10.1016/j.chom.2008.03.007
Published
2008-05-15
Pages
323-30
Language
English
Region
United States
NLM ID
101302316
PMCID
PMC2873178
Subset
IM
Grants
NIAID NIH HHS · R01 AI051667-08 · United States
NIAID NIH HHS · K08 AI076632 · United States
NIAID NIH HHS · P01 AI063302-030001 · United States
NIAID NIH HHS · P01 AI063302-068602 · United States
NIAID NIH HHS · P01 AI063302-020001 · United States
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NIAID NIH HHS · P01 AI063302 · United States
NIAID NIH HHS · P01 AI063302-010001 · United States
NIAID NIH HHS · R01 AI051667-06 · United States
NIAID NIH HHS · P01 AI063302-050001 · United States
NIAID NIH HHS · K08 AI076632-01A1 · United States
NIAID NIH HHS · K08 AI076632-02 · United States
NIAID NIH HHS · AI51667 · United States
NIAID NIH HHS · AI63302 · United States
NIAID NIH HHS · R01 AI051667-09 · United States
NIAID NIH HHS · R01 AI051667-07 · United States
NIAID NIH HHS · R01 AI051667 · United States
Databases
GEO
GSE10897
Corrections
CommentIn
PMID: 18474353
External Links
PubMed source DOI: 10.1016/j.chom.2008.03.007 PMC Full Text View journal details
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