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Metabolic dysfunction impairs Mycobacterium tuberculosis-specific cytokine and chemokine responses in latent tuberculosis and type 2 diabetes mellitus

  • Liu, Q. et al. The association between diabetes mellitus and the risk of latent tuberculosis infection: a systematic review and meta-analysis. Front. Med. 9, 899821 (2022).


    Google Scholar
     

  • Al-Rifai, R. H., Pearson, F., Critchley, J. A. & Abu-Raddad, L. J. Association between diabetes mellitus and active tuberculosis: A systematic review and meta-analysis. PLoS ONE 12(11), e0187967 (2017).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Huangfu, P., Ugarte-Gil, C., Golub, J., Pearson, F. & Critchley, J. The effects of diabetes on tuberculosis treatment outcomes: an updated systematic review and meta-analysis. Int. J. Tuberculosis Lung Dis. 23(7), 783–796 (2019).

    CAS 

    Google Scholar
     

  • Chen, H. et al. The impact of pulmonary tuberculosis on immunological and metabolic features of diabetic patients. Front. Immunol. 13, 973991 (2022).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rissaadah, S., Nursiswati, N. & Pahria, T. Glycemic profile and clinical treatment in patients with diabetes mellitus-tuberculosis: an update scoping review. J. Multidiscip. Healthc. 18, 747–758 (2025).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hensel, R. L. et al. Increased risk of latent tuberculous infection among persons with pre-diabetes and diabetes mellitus. Int. J. Tuberc. Lung Dis. 20(1), 71–78 (2016).

    CAS 
    PubMed 

    Google Scholar
     

  • Ssekamatte, P., Sande, O. J., van Crevel, R. & Biraro, I. A. Immunologic, metabolic and genetic impact of diabetes on tuberculosis susceptibility. Front. Immunol. 14, 1122255 (2023).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kumar, N. P. et al. Type 2 diabetes mellitus coincident with pulmonary tuberculosis is associated with heightened systemic type 1, type 17, and other proinflammatory cytokines. Ann. Am. Thorac. Soc. 10(5), 441–449 (2013).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kumar, N. P. et al. Diminished systemic and antigen-specific type 1, type 17, and other proinflammatory cytokines in diabetic and prediabetic individuals with latent Mycobacterium tuberculosis infection. J. Infect. Dis. 210(10), 1670–1678 (2014).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Domingo-Gonzalez, R., Prince, O., Cooper, A. & Khader, S. A. Cytokines and Chemokines in Mycobacterium tuberculosis Infection. Microbiol. Spectrum. 4(5), 23 (2016).


    Google Scholar
     

  • Ashenafi, S. et al. Progression of clinical tuberculosis is associated with a Th2 immune response signature in combination with elevated levels of SOCS3. Clin. Immunol. 151(2), 84–99 (2014).

    CAS 
    PubMed 

    Google Scholar
     

  • Ssekamatte, P. et al. Type 2 diabetes mellitus and latent tuberculosis infection moderately influence innate lymphoid cell immune responses in Uganda. Front. Immunol. 12, 3551 (2021).


    Google Scholar
     

  • Ritchie, M. E. et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43(7), e7-e (2015).


    Google Scholar
     

  • Wickham, H. ggplot2: Elegant Graphics for Data Analysis 2nd edn. (Springer, 2016).


    Google Scholar
     

  • Hu, R., Xia, C.-Q., Butfiloski, E. & Clare-Salzler, M. Effect of high glucose on cytokine production by human peripheral blood immune cells and type I interferon signaling in monocytes: Implications for the role of hyperglycemia in the diabetes inflammatory process and host defense against infection. Clin. Immunol. 195, 139–148 (2018).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Grossmann, V. et al. Profile of the immune and inflammatory response in individuals with prediabetes and type 2 diabetes. Diabetes Care 38(7), 1356–1364 (2015).

    CAS 
    PubMed 

    Google Scholar
     

  • Eckold, C. et al. Impact of intermediate hyperglycemia and diabetes on immune dysfunction in tuberculosis. Clin. Infect. Dis. 72(1), 69–78 (2020).

    PubMed Central 

    Google Scholar
     

  • Maciag, K., Plumlee, C. R., Cohen, S. B., Gern, B. H. & Urdahl, K. B. Reappraising the role of T cell-derived IFN-γ in restriction of mycobacterium tuberculosis in the murine lung. J. Immunol. 213(3), 339–346 (2024).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Green, A. M., DiFazio, R. & Flynn, J. L. IFN-γ from CD4 T Cells Is essential for host survival and enhances CD8 T cell function during mycobacterium tuberculosis infection. J. Immunol. 190(1), 270–277 (2013).

    CAS 
    PubMed 

    Google Scholar
     

  • Allie, N. et al. Prominent role for T cell-derived tumour necrosis factor for sustained control of mycobacterium tuberculosis infection. Sci. Rep. 3(1), 1809 (2013).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Clay, H., Volkman, H. E. & Ramakrishnan, L. Tumor necrosis factor signaling mediates resistance to mycobacteria by inhibiting bacterial growth and macrophage death. Immunity 29(2), 283–294 (2008).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Liu, X. et al. IL-2 restores T-cell dysfunction induced by persistent mycobacterium tuberculosis antigen stimulation. Front. Immunol. 10, 2350 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cooper, A. M., Magram, J., Ferrante, J. & Orme, I. M. Interleukin 12 (IL-12) is crucial to the development of protective immunity in mice intravenously infected with mycobacterium tuberculosis. J. Exp. Med. 186(1), 39–45 (1997).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chen, Y.-Y. et al. Recombinant bacille Calmette-Guerin coexpressing Ag85b, CFP10, and interleukin-12 elicits effective protection against Mycobacterium tuberculosis. J. Microbiol. Immunol. Infect. 50(1), 90–96 (2017).

    CAS 
    PubMed 

    Google Scholar
     

  • Roca, F. J., Whitworth, L. J., Redmond, S., Jones, A. A. & Ramakrishnan, L. TNF induces pathogenic programmed macrophage necrosis in tuberculosis through a mitochondrial-lysosomal-endoplasmic reticulum circuit. Cell 178(6), 1344–61.e11 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Blauenfeldt, T. et al. Interplay of DDP4 and IP-10 as a potential mechanism for cell recruitment to tuberculosis lesions. Front. Immunol. 9, 1456 (2018).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Taub, D. D., Turcovski-Corrales, S. M., Key, M. L., Longo, D. L. & Murphy, W. J. Chemokines and T lymphocyte activation: Beta chemokines costimulate human T lymphocyte activation in vitro. J. Immunol. 156(6), 2095–2103 (1996).

    CAS 
    PubMed 

    Google Scholar
     

  • Karpus, W. J. et al. Differential CC chemokine-induced enhancement of T helper cell cytokine production. J. Immunol. 158(9), 4129–4136 (1997).

    CAS 
    PubMed 

    Google Scholar
     

  • Saukkonen, J. J. et al. β-chemokines are induced by mycobacterium tuberculosis and inhibit its growth. Infect. Immun. 70(4), 1684–1693 (2002).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • McNab, F. W. et al. Type I IFN Induces IL-10 production in an IL-27–independent manner and blocks responsiveness to IFN-γ for production of IL-12 and bacterial killing in mycobacterium tuberculosis–infected macrophages. J. Immunol. 193(7), 3600–3612 (2014).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kotov, D. I. et al. Early cellular mechanisms of type I interferon-driven susceptibility to tuberculosis. Cell 186(25), 5536–53.e22 (2023).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Permanyer, M. et al. Efficient IL-2R signaling differentially affects the stability, function, and composition of the regulatory T-cell pool. Cell. Mol. Immunol. 18(2), 398–414 (2021).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ristić-Djurović, J. L., Ćirković, S., Mladenović, P., Romčević, N. & Trbovich, A. M. Analysis of methods commonly used in biomedicine for treatment versus control comparison of very small samples. Comput. Methods Programs Biomed. 157, 153–162 (2018).

    PubMed 

    Google Scholar
     

  • Redford, P. S., Murray, P. J. & O’Garra, A. The role of IL-10 in immune regulation during M tuberculosis infection. Mucosal Immunol. 4(3), 261–270 (2011).

    CAS 
    PubMed 

    Google Scholar
     

  • Mishra, A. et al. Human macrophages exhibit GM-CSF dependent restriction of mycobacterium tuberculosis infection via regulating their self-survival. Diff. Metab. Front. Immunol. 13, 859116 (2022).

    CAS 

    Google Scholar
     

  • Fremond, C. M. et al. IL-1 receptor-mediated signal is an essential component of MyD88-dependent innate response to mycobacterium tuberculosis infection. J. Immunol. 179(2), 1178–1189 (2007).

    CAS 
    PubMed 

    Google Scholar
     

  • Mayer-Barber, K. D. et al. Cutting edge: Caspase-1 Independent IL-1β Production Is critical for host resistance to mycobacterium tuberculosis and does not require TLR signaling in vivo. J. Immunol. 184(7), 3326–3330 (2010).

    CAS 
    PubMed 

    Google Scholar
     

  • Moreira-Teixeira, L. et al. T cell-derived IL-10 impairs host resistance to mycobacterium tuberculosis infection. J. Immunol. 199(2), 613–623 (2017).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Park, H.-S. et al. Mycobacterium tuberculosis Rv2145c promotes intracellular survival by STAT3 and IL-10 receptor signaling. Front. Immunol. 12, 666293 (2021).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sinha, R. et al. Pre-diabetes increases tuberculosis disease severity, while high body fat without impaired glucose tolerance is protective. Front. Cell. Infect. Microbiol. 11, 691823 (2021).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tan, K. S. et al. Glutathione deficiency in type 2 diabetes impairs cytokine responses and control of intracellular bacteria. J. Clin. Invest. 122(6), 2289–2300 (2012).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Restrepo, B. I. et al. Tuberculosis in poorly controlled type 2 diabetes: altered cytokine expression in peripheral white blood cells. Clin. Infect. Dis. 47(5), 634–641 (2008).

    CAS 
    PubMed 

    Google Scholar
     

  • Pooran, A. et al. IL-4 subverts mycobacterial containment in Mycobacterium tuberculosis-infected human macrophages. Eur. Respir. J. 54(2), 1802242 (2019).

    CAS 
    PubMed 

    Google Scholar
     

  • Krupa, A. et al. Binding of CXCL8/IL-8 to Mycobacterium tuberculosis modulates the innate immune response. Mediators inflamm. 1, 124762 (2015).


    Google Scholar
     

  • Amersfoort, J. et al. Diet-induced dyslipidemia induces metabolic and migratory adaptations in regulatory T cells. Cardiovasc. Res. 117(5), 1309–1324 (2020).

    PubMed Central 

    Google Scholar
     

  • Varshney, P., Yadav, V. & Saini, N. Lipid rafts in immune signalling: current progress and future perspective. Immunology 149(1), 13–24 (2016).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Legler, D. F., Micheau, O., Doucey, M.-A., Tschopp, J. & Bron, C. Recruitment of TNF receptor 1 to lipid rafts is essential for TNFα-Mediated NF-κB activation. Immunity 18(5), 655–664 (2003).

    CAS 
    PubMed 

    Google Scholar
     

  • Sen, S., Roy, K., Mukherjee, S., Mukhopadhyay, R. & Roy, S. Restoration of IFNγR subunit assembly, IFNγ signaling and parasite clearance in Leishmania donovani Infected Macrophages: role of membrane cholesterol. PLoS Pathog. 7(9), e1002229 (2011).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ross, S. H. & Cantrell, D. A. Signaling and function of Interleukin-2 in T lymphocytes. Ann. Rev. Immunol. 36, 411–433 (2018).

    CAS 

    Google Scholar
     

  • Bensussen, A., Santana, M. A. & Rodríguez-Jorge, O. Metabolic alterations impair differentiation and effector functions of CD8+ T cells. Front Immunol. 13, 945980 (2022).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mahammad, S., Dinic, J., Adler, J. & Parmryd, I. 2010 Limited cholesterol depletion causes aggregation of plasma membrane lipid rafts inducing T cell activation Biochimica et Biophysica Acta (BBA). Mol. Cell Biol. Lipids. 6, 625–634 (1801).


    Google Scholar
     

  • Zhu, Y. et al. lowering Glycosphingolipid levels in CD4+ T cells attenuates T cell receptor signaling, cytokine production, and differentiation to the Th17 lineage. J. Biol. Chem. 286(17), 14787–14794 (2011).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lokpo, S. Y. et al. The pattern of dyslipidaemia and factors associated with elevated levels of non-HDL-cholesterol among patients with type 2 diabetes mellitus in the Ho municipality: A cross sectional study. Heliyon. 8, 8 (2022).


    Google Scholar
     

  • Abdissa, D. & Hirpa, D. Dyslipidemia and its associated factors among adult diabetes outpatients in West Shewa zone public hospitals, Ethiopia. BMC Cardiovasc. Disord. 22(1), 39 (2022).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Brake, J. et al. Inflammation and dyslipidaemia in combined diabetes and tuberculosis; a cohort study. iScience. 28, 112760 (2025).

    PubMed 
    PubMed Central 

    Google Scholar
     

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