title: Coincident diabetes mellitus modulates Th1-, Th2-, and Th17-cell responses in latent tuberculosis in an IL-10- and TGF-β-dependent manner.
abstract: Type 2 diabetes mellitus (DM) is a risk factor for the development of active tuberculosis (TB), although its role in the TB-induced responses in latent TB (LTB) is not well understood. Since Th1, Th2, and Th17 responses are important in immunity to LTB, we postulated that coincident DM could alter the function of these CD4(+) T-cell subsets. To this end, we examined mycobacteria-induced immune responses in the whole blood of individuals with LTB-DM and compared them with responses of individuals without DM (LTB-NDM). T-cell responses from LTB-DM are characterized by diminished frequencies of mono- and dual-functional CD4(+) Th1, Th2, and Th17 cells at baseline and following stimulation with mycobacterial antigens-purified protein derivative, early secreted antigen-6, and culture filtrate protein-10. This modulation was at least partially dependent on IL-10 and TGF-β, since neutralization of either cytokine resulted in significantly increased frequencies of Th1 and Th2 cells but not Th17 cells in LTB-DM but not LTB individuals. LTB-DM is therefore characterized by diminished frequencies of Th1, Th2, and Th17 cells, indicating that DM alters the immune response in latent TB leading to a suboptimal induction of protective CD4(+) T-cell responses, thereby providing a potential mechanism for increased susceptibility to active disease.
authors.affiliation: National Institutes of Health-NIRT-International Center for Excellence in Research, Chennai, India.
authors.forename: Nathella Pavan
authors.initials: NP
authors.lastname: Kumar
authors.affiliation: National Institutes of Health-NIRT-International Center for Excellence in Research, Chennai, India.
authors.forename: Kadar
authors.initials: K
authors.lastname: Moideen
authors.affiliation: National Institutes of Health-NIRT-International Center for Excellence in Research, Chennai, India.
authors.forename: Parakkal Jovvian
authors.initials: PJ
authors.lastname: George
authors.affiliation: National Institute for Research in Tuberculosis, Chennai, India.
authors.forename: Chandrakumar
authors.initials: C
authors.lastname: Dolla
authors.affiliation: National Institute for Research in Tuberculosis, Chennai, India.
authors.forename: Paul
authors.initials: P
authors.lastname: Kumaran
authors.affiliation: National Institutes of Health-NIRT-International Center for Excellence in Research, Chennai, India.
authors.forename: Subash
authors.initials: S
authors.lastname: Babu
mesh_terms: D000328:Adult; D000368:Aged; D057134:Antibodies, Neutralizing / Q000378:metabolism; D000942:Antigens, Bacterial / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000276:immunology*; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D055985:Latent Tuberculosis / Q000150:complications / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C553218:CFP-10 protein, Mycobacterium bovis; D016212:Transforming Growth Factor beta; D016753:Interleukin-10
keywords: Diabetes ⋅ IL-10 ⋅ Tuberculosis ⋅ Th cells ⋅ TGF-β