Kawahara Tomohiro, Takahashi Tadanobu, Oishi Kenta, Tanaka Hiromu, Masuda Midori, Takahashi Shunsaku, Takano Maiko, Kawakami Tatsuya, Fukushima Keijo, Kanazawa Hiroaki, Suzuki Takashi
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.
Microbiol Immunol. 2015 Jan;59(1):1-12. doi: 10.1111/1348-0421.12210.
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.
双歧杆菌是肠道微生物群的主要组成部分之一,作为一种益生菌显示出抗流感病毒(IFV)的潜力,部分原因是通过调节肠道免疫系统增强先天免疫力。长双歧杆菌MM-2(MM-2)是一种对人类非常安全的细菌,从健康人体中分离得到,并在小鼠模型中显示出其对IFV感染的保护作用。在经鼻接种IFV的小鼠中,连续17天口服MM-2可改善临床症状、降低死亡率、抑制下呼吸道炎症,并降低支气管肺泡灌洗液中的病毒滴度、细胞死亡以及促炎细胞因子如IL-6和TNF-α的水平。MM-2的抗IFV机制涉及先天免疫,通过显著增加肺和脾中的NK细胞活性以及显著增加NK细胞激活剂如IFN-γ、IL-2、IL-12和IL-18的肺基因表达来实现。即使在未感染的小鼠中,给予MM-2也能显著增强派尔集合淋巴结细胞(PPs)产生IFN-γ的能力以及脾NK细胞的活性。连续17天口服MM-2可激活PPs中的全身免疫反应性,这有助于包括NK细胞激活在内的先天免疫,从而产生抗IFV作用。MM-2作为一种益生菌可能在IFV流行的管理中作为预防剂发挥作用。