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Unique Chemokine Profiles of Lung Tissues Distinguish Post-chemotherapeutic Persistent and Chronic Tuberculosis in a Mouse Model

 Soomin Park  ;  Seung-Hun Baek  ;  Sang-Nae Cho  ;  Young-Saeng Jang  ;  Ahreum Kim  ;  In-Hong Choi 
 Frontiers in Cellular and Infection Microbiology, Vol.7 : 314, 2017 
Journal Title
 Frontiers in Cellular and Infection Microbiology 
Issue Date
Animals ; Antitubercular Agents/administration & dosage ; Chemokines/genetics* ; Chemokines/immunology ; Chronic Disease ; Disease Models, Animal ; Gene Expression Profiling ; Humans ; Latent Tuberculosis/genetics ; Latent Tuberculosis/immunology ; Latent Tuberculosis/microbiology* ; Lung/immunology* ; Lung/microbiology ; Mice ; Mycobacterium tuberculosis/physiology* ; Tuberculosis/drug therapy* ; Tuberculosis/genetics* ; Tuberculosis/immunology ; Tuberculosis/microbiology
active tuberculosis ; cDNA microarrays ; chemokines ; lung tissues ; mouse model ; persistent tuberculosis
There is a substantial need for biomarkers to distinguish latent stage from active Mycobacterium tuberculosis infections, for predicting disease progression. To induce the reactivation of tuberculosis, we present a new experimental animal model modified based on the previous model established by our group. In the new model, the reactivation of tuberculosis is induced without administration of immunosuppressive agents, which might disturb immune responses. To identify the immunological status of the persistent and chronic stages, we analyzed immunological genes in lung tissues from mice infected with M. tuberculosis. Gene expression was screened using cDNA microarray analysis and confirmed by quantitative RT-PCR. Based on the cDNA microarray results, 11 candidate cytokines genes, which were obviously up-regulated during the chronic stage compared with those during the persistent stage, were selected and clustered into three groups: (1) chemokine genes, except those of monocyte chemoattractant proteins (MCPs; CXCL9, CXCL10, CXCL11, CCL5, CCL19); (2) MCP genes (CCL2, CCL7, CCL8, CCL12); and (3) TNF and IFN-γ genes. Results from the cDNA microarray and quantitative RT-PCR analyses revealed that the mRNA expression of the selected cytokine genes was significantly higher in lung tissues of the chronic stage than of the persistent stage. Three chemokines (CCL5, CCL19, and CXCL9) and three MCPs (CCL7, CCL2, and CCL12) were noticeably increased in the chronic stage compared with the persistent stage by cDNA microarray (p < 0.01, except CCL12) or RT-PCR (p < 0.01). Therefore, these six significantly increased cytokines in lung tissue from the mouse tuberculosis model might be candidates for biomarkers to distinguish the two disease stages. This information can be combined with already reported potential biomarkers to construct a network of more efficient tuberculosis markers.
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1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, A Rum(김아름)
Cho, Sang Nae(조상래)
Choi, In Hong(최인홍) ORCID logo https://orcid.org/0000-0001-9851-0137
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