Increased resistin may suppress reactive oxygen species production and inflammasome activation in type 2 diabetic patients with pulmonary tuberculosis infection.

Although it has been known for decades that patients with type 2 diabetes mellitus (DM) are more susceptible to severe tuberculosis (TB) infection, the underlying immunological mechanisms remain unclear. Resistin, a protein produced by immune cells in humans, causes insulin resistance and has been implicated in inhibiting reactive oxygen species (ROS) production in leukocytes. Recent studies suggested that IL-1β production in patients with Mycobacteria tuberculosis infection correlates with inflammasome activation which may be regulated by ROS production in the immune cells. By investigating the level of resistin in different patient groups, we found that serum resistin levels were significantly higher in severe TB and DM-only groups when compared with mild TB cases and healthy controls. Moreover, elevation of serum resistin correlated with impairment of ROS production of neutrophils in patients with both DM and TB. In human macrophages, exogenous resistin inhibits the production of ROS which are important in the mycobacterium-induced inflammasome activation. Moreover, macrophages with defective ROS production had poor IL-1β production and ineffective control of mycobacteria growth. Our results suggest that increased resistin in severe TB and DM patients may suppress the mycobacterium-induced inflammasome activation through inhibiting ROS production by leukocytes.