Differential immune response of adipocytes to virulent and attenuated Mycobacterium tuberculosis

Abstract

Mycobacterium tuberculosis ( M. tb) takes advantage of various cell types, allowing it to remain in the host for long periods. Because adipocytes have been proposed as niches for dormant M. tb in the latent state, understanding the interaction of virulent M. tb with adipocytes is important. We compared changes in cytokine secretion from 3T3-L1 murine adipocytes infected with virulent M. tb H37Rv (V- M. tb) and attenuated M. tb H37Ra (A- M. tb) strains. Both strains maintained non-replicating states within adipocytes until 10 days post-infection. Adipocytes infected with V- M. tb secreted lower levels of pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-12p40, IL-6, and IL-17, and lower levels of nitric oxide than those infected with A- M. tb. In contrast, the anti-inflammatory cytokines, IL-10 and IL-4, were markedly induced in V -M. tb-infected adipocytes versus those infected with A -M. tb at an early time point. Heat-killed or formalin-fixed bacteria induced lower levels of cytokines and no difference was observed between strains. Moreover, V- M. tb induced a high level of necrosis versus A -M. tb in conjunction with increased levels of LHD. These results suggest that V- M. tb regulates cytokine expression in its favor, increasing cytokines necessary for immune evasion and decreasing those required for protective immunity.