Progression of clinical tuberculosis is associated with a Th2 immune response signature in combination with elevated levels of SOCS3

- Comprehensive assessment of local cytokine profiles in human TB
- Low Th1, but increased IL-4, CCL4 and SOCS3 in patients with pulmonary TB
- A Th2 response in lung TB correlates to elevated mycobacteria-specific IgG titres
- Induction of SOCS1 and 3 in human cells after infection with M. tuberculosis
- Excess SOCS expression may promote a Th1/Th2 imbalance in progressive TB disease

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.