Primary Role of Suppressor of Cytokine Signaling 1 in Mycobacterium bovis BCG Infection

• Published in: Infection and immunity 2018-11, Vol.86 (11)
• Main Authors: Soma, Shogo, Kawai, Satoru, Inada, Hiroyasu, Watanabe, Kenta, Mizuno, Satoru, Kato, Seiichi, Matsuo, Kazuhiro, Yasutomi, Yasuhiro
• Format: Article
• Language: English
• Subjects: Animals; Cellular Microbiology: Pathogen-Host Cell Molecular Interactions; Disease Models, Animal; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Host-Pathogen Interactions; Mice, Inbred C57BL; Mice, Knockout; Mycobacterium bovis - growth & development; Nitric Oxide - metabolism; Nitric Oxide Synthase Type II - deficiency; Nitric Oxide Synthase Type II - metabolism; Signal Transduction; Suppressor of Cytokine Signaling 1 Protein - genetics; Suppressor of Cytokine Signaling 1 Protein - metabolism; Tuberculosis - microbiology; Tuberculosis - pathology
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/iai.00376-18

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-Guérin 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 that 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 nitric oxide (NO) production to establish mycobacterial infection and that rBCG-SOCS1DN has the potential to be a powerful tool for studying the primary function of SOCS1 in mycobacterial infection.