Figure 3.

The proposed role of resolvin D1 (RvD1) in leprosy. (Left side) The levels of RvD1 (dotted line) are higher before the start (T0) of multidrug therapy (MDT). The higher levels of RvD1 are hypothesized to increase the host’s susceptibility to M. leprae infection. The increased levels of RvD1 prior to MDT could enhance the capacity of macrophages to engulf M. leprae antigens as well as the pathogen itself via efferocytosis. This would lead to antigen clearance, decreased antigen stimulation of T-helper type 1 (Th1) and T-helper type 17 (Th17) cells and favor the survival of M. leprae. Moreover, increased levels of RvD1 could directly inhibit Th1 and Th17 cells’ response and promote the activity of T regulatory (Treg) cells. (Right side) After the start of MDT, the levels of RvD1 decrease (dotted line), while the abundance of M. leprae antigens increase (solid line) due to lysis and degradation of the bacilli, especially in multi-bacillary patients. The reduction of RvD1 could eliminate the suppression of the Th1 and Th17 responses, reduce the activation of Treg cells, and also decrease the ability of macrophages to promote efferocytosis. This impairment in efferocytosis would favor antigen accumulation. Thus, response to mycobacterial antigens by Th1 and Th17 cells would increase resulting in an immune-inflammatory response and potentially a T1R. The red color represents an intensification or increase in a process or abundance of a product, while the blue color symbolizes an attenuation of the process or product abundance. Arrows with solid lines indicate that a process related to the associated RvD1 level is favored, while an arrow with a hashed line indicates the process is not favored. (⊢) Represents inhibition of a process or activity. MΦ1 – M1, pro-inflammatory macrophages.