Primary role of suppressor of cytokine signaling 1 in Mycobacterium bovis BCG infection

Suppressor of cytokine signaling 1 (SOCS1) is a negative regulator of JAK/STAT signaling and is induced by mycobacterial infection. To understand the major function of SOCS1 during infection, we established a novel system in which recombinant Bacillus Calmette-Guerin expressed dominant-negative SOCS1 (rBCG-SOCS1DN) because it would not affect the function of SOCS1 in uninfected cells. When C57BL/6 mice and Rag1 -/- mice were intratracheally inoculated with rBCG-SOCS1DN, the amount of rBCG-SOCS1DN in the lungs was significantly reduced compared to the amounts in the lungs of mice inoculated with a vector control counterpart and wild-type BCG. However, these significant differences were not observed in Nos2 -/- mice and Rag1 -/- Nos2 -/- double-knockout mice. These findings demonstrated that SOCS1 inhibits NO production to establish mycobacterial infection and the rBCG-SOCS1DN has the potential to be a powerful tool for studying the primary function of SOCS1 in mycobacterial infection.