Identification and Functional analysis of Gene Expression in Mycobacterium tuberculosis-infected Human Monocytic Cells Under Hypoxic Conditions

ABSTRACT

Mycobacterium tuberculosis-induced granulomatous lesions, particularly those undergoing central caseation, are known as hypoxic. To analyze the host genes associated with hypoxic conditions from cells infected with M. tuberculosis, we performed GeneChip analyses on mRNA from M. tuberculosis H37Rv-treated human monocytic THP-1 cells cultured in oxygen-depleted status for 18 h. The expression of 99 genes was altered, including those involved in intracellular signaling, energy production, and protein metabolism, as revealed by stringent microarray data analysis. Most notably, mRNA expression of chemokine macrophage inflammatory protein 3alpha/CC chemokine ligand 20 (CCL20) was significantly up-regulated in M. tuberculosis-infected cells under hypoxic conditions. We further analyzed the CCL20 expression in peripheral blood mononuclear cells (PBMCs) and monocyte derived macrophages (MDMs) from healthy controls and TB patients. A comparative analysis has revealed that the mRNA and protein expression of CCL20 were prominently up-regulated in PBMCs, and MDMs from TB patients, compared with healthy controls. Collectively, these data show that the gene expression of CCL20 was up-regulated in M. tuberculosis H37Rv-infected human monocytic THP-1 cells cultured in hypoxic conditions. In addition, the production of CCL20 is substantially increased in cells from TB patients than in healthy controls, suggesting an important role of CCL20 in the immunopathogenesis during TB infection.