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Infect Immun. 2018 Oct 25;86(11). pii: e00376-18. doi: 10.1128/IAI.00376-18. Print 2018 Nov.

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

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Department of Molecular and Experimental Medicine, Mie University Graduate School of Medicine, Edobashi, Tsu, Mie, Japan.
Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition, Tsukuba, Ibaraki, Japan.
Department of Tropical Medicine and Parasitology, Dokkyo Medical University, Mibu, Shimotsuga, Tochigi, Japan.
Faculty of Pharmaceutical Science, Department of Pathology, Suzuka University of Medical Science, Minamitamagaki, Suzuka, Mie, Japan.
Joint Faculty of Veterinary Medicine, Laboratory of Veterinary Public Health, Yamaguchi University, Oaza Yoshida, Yamaguchi, Japan.
Research and Development Department, Japan BCG Laboratory, Matsuyama, Kiyose, Tokyo, Japan.
Department of Molecular and Experimental Medicine, Mie University Graduate School of Medicine, Edobashi, Tsu, Mie, Japan


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 Mycobacterium bovis 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.


Mycobacterium bovis BCG; Mycobacterium tuberculosis; SOCS1; nitric oxide; recombinant BCG

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