ABSTRACT
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-1α 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-γ (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.
ABSTRACT
PURPOSE: This study was conducted to understand the in vivo and in vitro immune responses and to find whether there exists any difference in the systemic and localized immune responses in tuberculous pleuritis. METHODS: The in vivo levels of IFN-gamma and IL-4 were compared in plasma (BL) and pleural fluid (PF) of 47 tuberculous (TB) and 31 nontuberculous pleuritis (Non-TB) patients. In vitro cytokine response to various mycobacterial antigens was studied in 19 TB patients by ELISA. Both ex vivo and in vitro cytokine responses were further ascertained by intracellular cytokine staining on purified CD4+ T cells from pleural fluid mononuclear cells (PFMC) of 10 TB patients. RESULTS: The ex vivo results showed a significant increase in IFN-gamma levels and higher IFN-gamma + T cells in PF. On the other hand, in vitro results showed simultaneous increase in both IFN-gamma and IL-4 levels in the supernatants of antigen stimulated PFMC. Similarly antigen specific increase was observed in both IFN-gamma + and IL-4+ T cells in all cultured conditions. However, the percentile increase was more in IL-4 secreting T cells, significant for PPD stimulation (P < 0.05), indicating that in vitro cellular response was dominated by Th2 type. CONCLUSIONS: These results showed a differential T-helper response in TB pleuritis suggestive of predominant Th1 in vivo and mixed response (Th1 and Th2) under in vitro conditions.