Consecutive oral administration of Bifidobacterium longum MM-2 improves the defense system against influenza virus infection by enhancing natural killer cell activity in a murine model.
Bifidobacterium, one of the major components of intestinal microflora, shows anti-influenza virus (IFV) potential as a probiotic, partly through enhancement of innate immunity by modulation of the intestinal immune system. Bifidobacterium longum MM-2 (MM-2), a very safe bacterium in humans, was isolated from healthy humans and its protective effect against IFV infection in a murine model shown. In mice that were intranasally inoculated with IFV, oral administration of MM-2 for 17 consecutive days improved clinical symptoms, reduced mortality, suppressed inflammation in the lower respiratory tract, and decreased virus titers, cell death, and pro-inflammatory cytokines such as IL-6 and TNF-α in bronchoalveolar lavage fluid. The anti-IFV mechanism of MM-2 involves innate immunity through significant increases in NK cell activities in the lungs and spleen and a significant increase in pulmonary gene expression of NK cell activators such as IFN-γ, IL-2, IL-12 and IL-18. Even in non-infected mice, MM-2 administration also induced significant enhancement of both IFN-γ production by Peyer's patch cells (PPs) and splenetic NK cell activity. Oral administration of MM-2 for 17 days activates systemic immunoreactivity in PPs, which contributes to innate immunity, including NK cell activation, resulting in an anti-IFV effect. MM-2 as a probiotic may function as a prophylactic agent in the management of an IFV epidemic.
Department of Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan; Biofermin Kobe Research Institute, Biofermin Pharmaceutical, 7-3-4 Ibukidai-Higashimachi, Nishi-ku, Kobe, 651-2242, Japan.
Tomohiro
T
Kawahara
Tadanobu
T
Takahashi
Kenta
K
Oishi
Hiromu
H
Tanaka
Midori
M
Masuda
Shunsaku
S
Takahashi
Maiko
M
Takano
Tatsuya
T
Kawakami
Keijo
K
Fukushima
Hiroaki
H
Kanazawa
Takashi
T
Suzuki
D000284:Administration, Oral; D000818:Animals; D001644:Bifidobacterium / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000473:pathology; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000473:pathology; D019936:Probiotics / Q000008:administration & dosage*; D013154:Spleen / Q000276:immunology; D013415:Sulfalene; D016019:Survival Analysis
D016207:Cytokines; D013415:Sulfalene
Bifidobacterium longum; influenza virus; natural killer cell; probiotics