Differential Early Secreted Antigen Target (ESAT) 6 kDa–induced IFN-γ and SOCS1 expression distinguishes latent and active tuberculosis

Abstract

Introduction: Expression of Suppressor of cytokine signaling (SOCS)-1 molecules is increased in patients with tuberculosis (TB). Early Secreted Antigen Target (ESAT)-6 kDa -induced IFN-γ responses indicate Mycobacterium tuberculosis infection. The effect of ESAT6-stimulation on SOCS1 in the host is not known. Methodology: Healthy asymptomatic controls had a negative (n = 16) or a positive ( n = 13) tuberculin skin test (TST). ESAT6-induced IFN-γ responses classified these controls as positive (EC ESAT6 IFN-γ (+), n = 5) or negative (EC ESAT6 IFN-γ (-), n = 24) responders. Patients had pulmonary (n = 21) or extra-pulmonary (n = 30) tuberculosis. Peripheral blood cells were stimulated with ESAT6 and mRNA expression of IFN-γ and SOCS1 was determined. Results: ESAT6-induced IFN-γ expression was raised in EC ESAT6 IFN-γ (+) as compared with EC ESAT6 IFN-γ (-), p = 0.019. ESAT6-induced SOCS1 mRNA expression was increased in both pulmonary TB and extra-pulmonary TB patients as compared with both EC groups. ESAT6-induced IFN-γ/SOCS1 mRNA expression ratio was decreased in TB patients as compared with both EC groups. Conclusion: M. tuberculosis infection induces increased ESAT6-induced IFN-γ responses in both latent and active TB. Our data shows down-regulation of IFN-γ / SOCS1 expression to be induced only in active TB cases, distinguishing them from healthy individuals likely to have latent TB. A decreasing IFN-γ /SOCS1 ratio may leads to reduced Th1 immunity which contributes to inability of the host to control clinical disease.

Changed immune and miRNA response in RAW264.7 cells infected with cell wall deficient mycobacterium tuberculosis

“…It was reported that miR-29 was increased in serum, sputum and CD4 + T cells from active TB patients (14,15,44), which suggested that miR-29 plays important roles in TB infection. It has been demonstrated that IFN-γ is associated with latent TB infection and is a direct target of miR-29b (23,24,45,46). Our data showed that an increased miR-29b level was concomitant with a decreased IFN-γ expression in CWD-Mtb group compared with wild Mtb group.…”

MiR‐342 controls Mycobacterium tuberculosis susceptibility by modulating inflammation and cell death

“…SOCS proteins are negative regulators of the JAK/STAT pathway (Alexander & Hilton, 2004), and accumulating evidence indicates that they are involved in the control of the cytokine networks responsible for adequate and efficient innate immune responses (Yoshimura et␣al , 2007). For example, SOCS1 expression is significantly increased in patients with tuberculosis, where SOCS1 transcript levels are correlated with disease severity (Masood et␣al , 2012; Masood et␣al , 2013; Masood et␣al , 2014). SOCS1, 4, and 5 are highly expressed in mice infected with hypervirulent Mtb (Manca et␣al , 2005).…”