title: 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.
authors.affiliation: Department of Microbiology and Research Institute for Medical Sciences, Research Center for Endocrine and Metabolic Diseases, South Korea.
authors.forename: Jong-Seok
authors.initials: JS
authors.lastname: Kim
authors.forename: Min-Jeong
authors.initials: MJ
authors.lastname: Ryu
authors.forename: Eui-Hong
authors.initials: EH
authors.lastname: Byun
authors.forename: Woo Sik
authors.initials: WS
authors.lastname: Kim
authors.forename: Jake
authors.initials: J
authors.lastname: Whang
authors.forename: Ki-Nam
authors.initials: KN
authors.lastname: Min
authors.forename: Minho
authors.initials: M
authors.lastname: Shong
authors.forename: Hwa-Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Sung Jae
authors.initials: SJ
authors.lastname: Shin
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000276:immunology* / Q000382:microbiology; D000818:Animals; D015153:Blotting, Western; D005110:Extracellular Space / Q000737:chemistry; D005557:Formaldehyde; D006358:Hot Temperature; D006801:Humans; D057131:Immune Evasion; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D007770:L-Lactate Dehydrogenase / Q000032:analysis / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
chemical_list: D053762:Interleukin-12 Subunit p40; D020381:Interleukin-17; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D005557:Formaldehyde; D015847:Interleukin-4; D007770:L-Lactate Dehydrogenase