1. Progression of clinical tuberculosis is associated with a Th2 immune response signature in combination with elevated levels of SOCS3
- Author
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Amsalu Bekele, Getachew Aseffa, Meseret Habtamu, Jan Andersson, Susanna Brighenti, Maria Wijkander, Getachew Aderaye, Berit Carow, Martin E. Rottenberg, Martha Zewdie, Mattias Svensson, Abraham Aseffa, Anh Thu Nguyen Hoang, and Senait Ashenafi
- Subjects
Adult ,Male ,Chemokine ,Tuberculosis ,Adolescent ,medicine.medical_treatment ,Immunology ,HIV Infections ,Suppressor of Cytokine Signaling Proteins ,CCL5 ,Mycobacterium tuberculosis ,Young Adult ,Th2 Cells ,medicine ,Humans ,Immunology and Allergy ,RNA, Messenger ,SOCS3 ,Immune response ,Tuberculosis, Pulmonary ,Cells, Cultured ,Aged ,medicine.diagnostic_test ,biology ,Suppressor of cytokine signaling 1 ,business.industry ,Macrophages ,HIV ,Middle Aged ,biology.organism_classification ,medicine.disease ,Bronchoalveolar lavage ,Cytokine ,Gene Expression Regulation ,Suppressor of Cytokine Signaling 3 Protein ,Disease Progression ,Leukocytes, Mononuclear ,biology.protein ,Cytokines ,Female ,business ,Human - 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.
- Published
- 2014
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