title: A rho GDP dissociation inhibitor produced by apoptotic T-cells inhibits growth of Mycobacterium tuberculosis.
abstract: In this study, we found that a subpopulation of CD4(+)CD25(+) (85% Foxp3(+)) cells from persons with latent tuberculosis infection (LTBI) inhibits growth of M. tuberculosis (M. tb) in human monocyte-derived macrophages (MDMs). A soluble factor, Rho GDP dissociation inhibitor (D4GDI), produced by apoptotic CD4(+)CD25(+) (85% Foxp3(+)) cells is responsible for this inhibition of M. tb growth in human macrophages and in mice. M. tb-expanded CD4(+C)D25(+)Foxp3(+)D4GDI(+) cells do not produce IL-10, TGF-β and IFN-γ. D4GDI inhibited growth of M. tb in MDMs by enhancing production of IL-1β, TNF-α and ROS, and by increasing apoptosis of M. tb-infected MDMs. D4GDI was concentrated at the site of disease in tuberculosis patients, with higher levels detected in pleural fluid than in serum. However, in response to M. tb, PBMC from tuberculosis patients produced less D4GDI than PBMC from persons with LTBI. M. tb-expanded CD4+CD25+ (85% Foxp3(+)) cells and D4GDI induced intracellular M. tb to express the dormancy survival regulator DosR and DosR-dependent genes, suggesting that D4GDI induces a non-replicating state in the pathogen. Our study provides the first evidence that a subpopulation of CD4(+)CD25(+) (85% Foxp3+) cells enhances immunity to M. tb, and that production of D4GDI by this subpopulation inhibits M. tb growth.
authors: Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Center, Tyler, Texas, United States of America.
authors: Sambasivan
authors: S
authors: Venkatasubramanian
authors: Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Center, Tyler, Texas, United States of America.
authors: Rohan
authors: R
authors: Dhiman
authors: Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Center, Tyler, Texas, United States of America.
authors: Padmaja
authors: P
authors: Paidipally
authors: Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Center, Tyler, Texas, United States of America.
authors: Satyanarayana S
authors: SS
authors: Cheekatla
authors: Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Center, Tyler, Texas, United States of America.
authors: Deepak
authors: D
authors: Tripathi
authors: Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Center, Tyler, Texas, United States of America.
authors: Elwyn
authors: E
authors: Welch
authors: Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Center, Tyler, Texas, United States of America.
authors: Amy R
authors: AR
authors: Tvinnereim
authors: Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
authors: Brenda
authors: B
authors: Jones
authors: University of Colorado Comprehensive Cancer Center, Aurora, Colorado, United States of America.
authors: Dan
authors: D
authors: Theodorescu
authors: Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Center, Tyler, Texas, United States of America.
authors: Peter F
authors: PF
authors: Barnes
authors: Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Center, Tyler, Texas, United States of America.
authors: Ramakrishna
authors: R
authors: Vankayalapati
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D018920:Coculture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D055985:Latent Tuberculosis / Q000276:immunology*; D008264:Macrophages / Q000382:microbiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D008875:Middle Aged; D009169:Mycobacterium tuberculosis; D060888:Real-Time Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology; D055815:Young Adult; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors / Q000276:immunology*
chemical_list: D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors