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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.

Author information

1
Department of Molecular and Experimental Medicine, Mie University Graduate School of Medicine, Edobashi, Tsu, Mie, Japan.
2
Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition, Tsukuba, Ibaraki, Japan.
3
Department of Tropical Medicine and Parasitology, Dokkyo Medical University, Mibu, Shimotsuga, Tochigi, Japan.
4
Faculty of Pharmaceutical Science, Department of Pathology, Suzuka University of Medical Science, Minamitamagaki, Suzuka, Mie, Japan.
5
Joint Faculty of Veterinary Medicine, Laboratory of Veterinary Public Health, Yamaguchi University, Oaza Yoshida, Yamaguchi, Japan.
6
Research and Development Department, Japan BCG Laboratory, Matsuyama, Kiyose, Tokyo, Japan.
7
Department of Molecular and Experimental Medicine, Mie University Graduate School of Medicine, Edobashi, Tsu, Mie, Japan yasutomi@nibiohn.go.jp.

Abstract

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.

KEYWORDS:

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

PMID:
30181351
PMCID:
PMC6204702
DOI:
10.1128/IAI.00376-18
[Indexed for MEDLINE]
Free PMC Article

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