title: Immune regulatory activities of early secreted antigenic target of 6-kD protein of Mycobacterium tuberculosis and implications for tuberculosis vaccine design.
abstract: Although ESAT-6 was originally identified as a strong T cell immunogen in short-term culture filtrate of Mtb, and has therefore been a candidate vaccine antigen for many years, recent work has demonstrated that ESAT-6 is also a virulence factor that mediates pathogenicity of Mtb. The studies described in this review suggest that ESAT-6 secreted by Mtb subverts host immunity by manipulating intracellular signaling pathways in macrophages and T cells, which are critical in protection against Mtb. Furthermore, ESAT-6 elicits pro-inflammatory responses that can be detrimental to the host. Understanding the molecular mechanisms through which ESAT-6 inhibits immunity will permit design of ESAT-6-based vaccine constructs that elicit protective immune responses with minimal negative effects.
authors.affiliation: Center for Pulmonary and Infectious Disease Control, The University of Texas Health Science Center, Tyler, TX 75708, USA. buka.samten@uthct.edu
authors.forename: Buka
authors.initials: B
authors.lastname: Samten
authors.forename: Xisheng
authors.initials: X
authors.lastname: Wang
authors.forename: Peter F
authors.initials: PF
authors.lastname: Barnes
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D015195:Drug Design; D006801:Humans; D008262:Macrophage Activation / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D032581:Tuberculosis Vaccines / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D032581:Tuberculosis Vaccines