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

To identify the immunological status of the persistent and chronic stages, we analysed immunological genes in lung tissues from mice infected with M. tuberculosis. Based on the cDNA microarray results, 11 candidate cytokine 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. We present a new experimental animal model, in which the reactivation of tuberculosis is induced without administration of immunosuppressive agents, which might disturb immune responses. From lung tissue of chronic or persistent stage of tuberculosis, gene expression was screened using cDNA microarray analysis and confirmed by quantitative RT-PCR.