Recombinant Mycobacterium bovis bacillus Calmette-Guérin expressing Ag85B-IL-7 fusion protein enhances IL-17A-producing innate γδ T cells

Shinya Hatano; Toshiki Tamura; Masayuki Umemura; Goro Matsuzaki; Naoya Ohara; Yasunobu Yoshikai

doi:10.1016/j.vaccine.2016.03.096

Recombinant Mycobacterium bovis bacillus Calmette-Guérin expressing Ag85B-IL-7 fusion protein enhances IL-17A-producing innate γδ T cells

Vaccine. 2016 May 11;34(22):2490-5. doi: 10.1016/j.vaccine.2016.03.096. Epub 2016 Apr 11.

Authors

Shinya Hatano¹, Toshiki Tamura², Masayuki Umemura³, Goro Matsuzaki³, Naoya Ohara⁴, Yasunobu Yoshikai⁵

Affiliations

¹ Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, 3-1-1, Maidaishi, Higashi-ku, Fukuoka 812-8582, Japan.
² Department of Microbiology, Leprosy Research Center, National Institute of Infectious Diseases, Tokyo 189-0002, Japan.
³ Molecular Microbiology Group, Department of Tropical Infectious Diseases, Center of Molecular Biosciences, Tropical Biosphere Research Center, University of the Ryukyus, Nishihara, Okinawa 903-0213, Japan.
⁴ Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Kita-ku, Okayama 700-8525, Japan.
⁵ Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, 3-1-1, Maidaishi, Higashi-ku, Fukuoka 812-8582, Japan. Electronic address: yoshikai@bioreg.kyushu-u.ac.jp.

PMID: 27079930
DOI: 10.1016/j.vaccine.2016.03.096

Abstract

Interleukin 7 (IL-7) has an important function in the development and maintenance of IL-17A+ γδ T cells. We here constructed a recombinant Mycobacterium bovis bacillus Calmette-Guérin expressing antigen 85B (Ag85B)-IL-7 fusion protein (rBCG-Ag85B-IL-7). The Ag85B-IL-7 fusion protein and IL-7 were detected in the bacterial lysate of rBCG-Ag85B-IL-7. rBCG-Ag85B-IL-7 was the same in number as control rBCG expressing Ag85B (rBCG-Ag85B) in the lung at the early stage after intravenous inoculation, whereas the numbers of IL-17A+ γδ T cells and Ag-specific Th1 cells were significantly higher in the lungs of mice inoculated with rBCG-Ag85B-IL-7 than those inoculated with rBCG-Ag85B. The Ag-specific Th1 cell response was impaired in mice lacking IL-17A+ γδ T cells after inoculation with rBCG-Ag85B-IL-7. Thus, rBCG-Ag85B-IL-7 increases the pool size of IL-17A+ γδ T cells, which subsequently augment the Th1 response to mycobacterial infection.

Keywords: BCG; Bacteria; Cytokines; IL-17A; IL-7; γδ T cells.

Publication types

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

MeSH terms

Acyltransferases / genetics*
Acyltransferases / immunology*
Animals
Antigens, Bacterial / genetics*
Antigens, Bacterial / immunology*
BCG Vaccine / genetics
BCG Vaccine / immunology
Bacterial Proteins / genetics*
Bacterial Proteins / immunology*
Cytokines / immunology
Immunity, Innate
Interleukin-17 / immunology*
Interleukin-7 / genetics*
Interleukin-7 / immunology
Lung / immunology
Lung / microbiology
Mice
Mice, Inbred C57BL
Mycobacterium bovis / genetics*
Mycobacterium bovis / growth & development
Mycobacterium bovis / immunology
Receptors, Antigen, T-Cell, gamma-delta / immunology
Recombinant Fusion Proteins / immunology
T-Lymphocyte Subsets / immunology*
Th1 Cells / immunology

Substances

Antigens, Bacterial
BCG Vaccine
Bacterial Proteins
Cytokines
Interleukin-17
Interleukin-7
Receptors, Antigen, T-Cell, gamma-delta
Recombinant Fusion Proteins
Acyltransferases
antigen 85B, Mycobacterium tuberculosis