title: Progression of clinical tuberculosis is associated with a Th2 immune response signature in combination with elevated levels of SOCS3.
abstract: In this study, we explored the local cytokine/chemokine profiles in patients with active pulmonary or pleural tuberculosis (TB) using multiplex protein analysis of bronchoalveolar lavage and pleural fluid samples. Despite increased pro-inflammation compared to the uninfected controls; there was no up-regulation of IFN-γ or the T cell chemoattractant CCL5 in the lung of patients with pulmonary TB. Instead, elevated levels of IL-4 and CCL4 were associated with high mycobacteria-specific IgG titres as well as SOCS3 (suppressors of cytokine signaling) mRNA and progression of moderate-to-severe disease. Contrary, IL-4, CCL4 and SOCS3 remained low in patients with extrapulmonary pleural TB, while IFN-γ, CCL5 and SOCS1 were up-regulated. Both SOCS molecules were induced in human macrophages infected with Mycobacterium tuberculosis in vitro. The Th2 immune response signature found in patients with progressive pulmonary TB could result from inappropriate cytokine/chemokine responses and excessive SOCS3 expression that may represent potential targets for clinical TB management.
authors.affiliation: Karolinska Institutet, Center for Infectious Medicine (CIM), F59, Department of Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden; Black Lion University Hospital and Addis Ababa University, Department of Pathology, Faculty of Medicine, Addis Ababa, Ethiopia.
authors.forename: Senait
authors.initials: S
authors.lastname: Ashenafi
authors.affiliation: Black Lion University Hospital and Addis Ababa University, Department of Internal Medicine, Faculty of Medicine, Addis Ababa, Ethiopia.
authors.forename: Getachew
authors.initials: G
authors.lastname: Aderaye
authors.affiliation: Black Lion University Hospital and Addis Ababa University, Department of Internal Medicine, Faculty of Medicine, Addis Ababa, Ethiopia.
authors.forename: Amsalu
authors.initials: A
authors.lastname: Bekele
authors.affiliation: Armauer Hansen Research Institute (AHRI), Addis Ababa, Ethiopia.
authors.forename: Martha
authors.initials: M
authors.lastname: Zewdie
authors.affiliation: Black Lion University Hospital and Addis Ababa University, Department of Radiology, Faculty of Medicine, Addis Ababa, Ethiopia.
authors.forename: Getachew
authors.initials: G
authors.lastname: Aseffa
authors.affiliation: Karolinska Institutet, Center for Infectious Medicine (CIM), F59, Department of Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Anh Thu Nguyen
authors.initials: AT
authors.lastname: Hoang
authors.affiliation: Karolinska Institutet, Department of Microbiology, Tumor and Cell Biology (MTC), Stockholm, Sweden.
authors.forename: Berit
authors.initials: B
authors.lastname: Carow
authors.affiliation: Armauer Hansen Research Institute (AHRI), Addis Ababa, Ethiopia.
authors.forename: Meseret
authors.initials: M
authors.lastname: Habtamu
authors.affiliation: Karolinska Institutet, Center for Infectious Medicine (CIM), F59, Department of Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Wijkander
authors.affiliation: Karolinska Institutet, Department of Microbiology, Tumor and Cell Biology (MTC), Stockholm, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Rottenberg
authors.affiliation: Armauer Hansen Research Institute (AHRI), Addis Ababa, Ethiopia.
authors.forename: Abraham
authors.initials: A
authors.lastname: Aseffa
authors.affiliation: Karolinska Institutet, Center for Infectious Medicine (CIM), F59, Department of Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden; Karolinska University Hospital Huddinge, Department of Medicine, Division of Infectious Diseases, Stockholm, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Andersson
authors.affiliation: Karolinska Institutet, Center for Infectious Medicine (CIM), F59, Department of Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Mattias
authors.initials: M
authors.lastname: Svensson
authors.affiliation: Karolinska Institutet, Center for Infectious Medicine (CIM), F59, Department of Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden. Electronic address: susanna.brighenti@ki.se.
authors.forename: Susanna
authors.initials: S
authors.lastname: Brighenti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000382:microbiology; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology*; D055815:Young Adult
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; C106644:SOCS3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins
keywords: Cytokines; HIV; Human; Immune response; Tuberculosis