Infection with prevalent clinical strains of Mycobacterium tuberculosis leads to differential maturation of monocyte derived dendritic cells

The link between innate and adaptive host immune response to Mycobacterium tuberculosis (M.tb) is driven by dendritic cells (DC). In this study, we examined the ability of prevalent clinical strains from south India (S7, S10) and laboratory strain H37Rv (Rv) to induce maturation of monocyte derived dendritic cells (MoDC). The phenotypic and functional changes of DC upon infection with different strains of M.tb were evaluated. It was observed that S7 and Rv strains partially hampered the maturation of MoDC as reflected by the low expression of maturation markers and co-stimulatory markers when compared to LPS stimulated MoDC. In contrast, strain S10 infected DC showed a marked increase in the expression of these markers. The functional property was investigated by the ability of infected MoDC to induce T-cell proliferation and to stimulate secretion of IFN-γ by CD4⁺T-cells. It was found that Rv and S7 infected MoDC were less efficient in inducing T-cell proliferation. The secretion of IL-12 by Rv and S7 infected MoDC was also found to be significantly lesser than LPS stimulated MoDC. On the other hand, S10 infected MoDC showed enhanced T-cell stimulation and cytokine secretion. Together these results indicate that there is a substantial variability in the capacity of M.tb clinical strains to induce maturation of DC which may be dependent upon their virulence.