Kinetics of chemokine secretion in human macrophages infected with various strains of Mycobacterium tuberculosis

Background and Purpose: It has been shown that chemokine secretion upon infection with Mycobacterium tuberculosis is influenced by the virulence of the strain, and it is suggested that virulence-associated differences in chemokine secretion contribute to the failure in containing the infection due to poor granuloma formation. Materials and Methods: In this study, we used prevalent M tuberculosis clinical strains (S7 and S10) to study the chemokine secretion profile in infected THP-1 cells and monocyte-derived macrophages (MDM) and compared this with the chemokine secretion induced by laboratory strains. Results: This study showed that comparatively lower levels of IP-10 were induced by clinical strains than by laboratory strains in both differentiated THP-1 and MDMs. The secretion of MIP-1a was also depressed but only in the THP-1 cells infected with clinical strains. This depressed chemokine secretion may hinder the movement of Th-1 cells from the periphery into the infection foci to control the infection. Correlation between IP-10 and IL-12p40 showed a negative relationship in control MDMs, while there was a positive correlation in all the infected strains, indicating their cooperative role in attracting and activating Th1 cells for a protective immune response at the site. This relationship was strain dependent, with avirulent H37Ra showing higher correlation, followed by the clinical strains and the virulent H37Rv. A positive correlation of IP-10 with IFN-gamma (S7 and H37Ra) and with IL-10 (H37Ra and H37Rv) suggested a definitive interplay of these molecules in infection. Conclusions: The chemokines secretion by infected THP-1 cells and MDMs was strain dependant and the lower induction by the clinical strains may indicate that the clinical strains maintain a quiescent nature to mislead the host immune system for their benefit.