title: SOCS3 and STAT3, major controllers of the outcome of infection with Mycobacterium tuberculosis.
abstract: In our review, we address the role of signal transducer and activator of transcription-3 (STAT3) and suppressor of cytokine signaling-3 (SOCS3) in the outcome of Mycobacterium tuberculosis infection, focusing on functions of these molecules in regulating the biology of myeloid and lymphoid cells. The STAT3 transcription factor has paradoxical roles: mainly activating an anti-inflammatory program in myeloid cells while promoting the differentiation and activation of inflammatory T cells. STAT3 is a major player in all phases of T cell responses, including T cell subset differentiation, T cell activation, and generation of memory. We review the roles of cytokines that activate, or are activated by, STAT3 during the infection with M. tuberculosis. SOCS3 inhibits STAT3 activation, by some but not all STAT3-activating cytokine receptors. Infection with M. tuberculosis also stimulates SOCS3 expression in phagocytes. Studies in different mouse models have proven the critical importance of SOCS3 in restraining inflammation and allowing optimal levels of protective immune responses against the infection. The accumulated data presented here suggest a relevant program coordinated by SOCS3 in different cell populations, which results in improved control of infection with M. tuberculosis. STAT3 and SOCS3 may thus be targeted to improve the control of infection with M. tuberculosis or the efficiency of vaccination.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, S-171 77 Stockholm, Sweden. Electronic address: Martin.Rottenberg@ki.se.
authors.forename: Martin E
authors.initials: ME
authors.lastname: Rottenberg
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, S-171 77 Stockholm, Sweden. Electronic address: Berit.Carow@ki.se.
authors.forename: Berit
authors.initials: B
authors.lastname: Carow
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology; D018121:Receptors, Cytokine / Q000235:genetics / Q000276:immunology; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D014397:Tuberculosis, Pulmonary / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000473:pathology
chemical_list: D016207:Cytokines; D018121:Receptors, Cytokine; C106644:SOCS3 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins
keywords: Dendritic cell; M. tuberculosis; Macrophage; SOCS3; STAT3; T cell