Strain specific transcriptional response in Mycobacterium tuberculosis infected macrophages

Cell Communication and Signaling

Research

Selvakumar Subbian¹  Mi-Sun Koo¹  Gilla Kaplan¹ 

[1] Laboratory of Mycobacterial Immunity and Pathogenesis, The Public Health Research Institute (PHRI) at the University of Medicine and Dentistry of New Jersey (UNDNJ), 225 Warren Street, 07103, Newark, New Jersey, USA;

关键词: Tuberculosis;    Bone marrow-derived macrophage;    Gene expression;    Global transcriptome;    Mycobacterium tuberculosis;    Macrophage activation pathway;    Host-pathogen interaction;    Immune response;    Lipid metabolism;    Intracellular stress response;   

DOI  :  10.1186/1478-811X-10-2

 received in 2011-12-19, accepted in 2012-01-26,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundTuberculosis (TB), a bacterial infection caused by Mycobacterium tuberculosis (Mtb) remains a significant health problem worldwide with a third of the world population infected and nearly nine million new cases claiming 1.1 million deaths every year. The outcome following infection by Mtb is determined by a complex and dynamic host-pathogen interaction in which the phenotype of the pathogen and the immune status of the host play a role. However, the molecular mechanism by which Mtb strains induce different responses during intracellular infection of the host macrophage is not fully understood. To explore the early molecular events triggered upon Mtb infection of macrophages, we studied the transcriptional responses of murine bone marrow-derived macrophages (BMM) to infection with two clinical Mtb strains, CDC1551 and HN878. These strains have previously been shown to differ in their virulence/immunogenicity in the mouse and rabbit models of pulmonary TB.ResultsIn spite of similar intracellular growth rates, we observed that compared to HN878, infection by CDC1551 of BMM was associated with an increased global transcriptome, up-regulation of a specific early (6 hours) immune response network and significantly elevated nitric oxide production. In contrast, at 24 hours post-infection of BMM by HN878, more host genes involved in lipid metabolism, including cholesterol metabolism and prostaglandin synthesis were up-regulated, compared to infection with CDC1551.In association with the differences in the macrophage responses to infection with the 2 Mtb strains, intracellular CDC1551 expressed higher levels of stress response genes than did HN878.ConclusionsIn association with the early and more robust macrophage activation, intracellular CDC1551 cells were exposed to a higher level of stress leading to increased up-regulation of the bacterial stress response genes. In contrast, sub-optimal activation of macrophages and induction of a dysregulated host cell lipid metabolism favored a less stressful intracellular environment for HN878. Our findings suggest that the ability of CDC1551 and HN878 to differentially activate macrophages during infection probably determines their ability to either resist host cell immunity and progress to active disease or to succumb to the host protective responses and be driven into a non-replicating latent state in rabbit lungs.

【 授权许可】

Unknown   
© Koo et al; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.