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

Shogo Soma; Satoru Kawai; Hiroyasu Inada; Kenta Watanabe; Satoru Mizuno; Seiichi Kato; Kazuhiro Matsuo; Yasuhiro Yasutomi

doi:10.1128/IAI.00376-18

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

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

Authors

Shogo Soma^{1

2}, Satoru Kawai³, Hiroyasu Inada⁴, Kenta Watanabe⁵, Satoru Mizuno^{1

6}, Seiichi Kato^{2

6}, Kazuhiro Matsuo⁶, Yasuhiro Yasutomi^{7

2}

Affiliations

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
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*

Substances

Homeodomain Proteins
Socs1 protein, mouse
Suppressor of Cytokine Signaling 1 Protein
RAG-1 protein
Nitric Oxide
Nitric Oxide Synthase Type II
Nos2 protein, mouse