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


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-1alpha 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.
Rajavelu
P
P
Department of Immunology, Tuberculosis Research Centre ICMR, Chennai 600031, India.
Das
S D
SD
D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism*; D006801:Humans; D057131:Immune Evasion; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology*; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D018417:Th1 Cells / Q000276:immunology
D018925:Chemokines