Probiotics are live bacteria that confer

a health benefit to the host when administrated in adequate amounts (WAO/WHO, 2002), and lactic acid bacteria (LAB) including lactobacilli and bifidobacteria are commonly used as probiotics. LAB exhibit a variety of immunomodulating effects, including preventive effects against various infections (Nomoto, 2005; Namba et al., 2010; Fukuda et al., 2011) and carcinogenesis (Reddy & Rivenson, 1993; Takagi et al., 2001) as well as antiallergic effects (Fujiwara et al., 2004; Xiao et al., 2006a ,b). Leyer et al. (2009) have reported that intake of the combination of probiotic strains reduced cold and influenza-like symptom incidence and duration in healthy children during the winter season. Several studies have demonstrated find more that some strains of LAB protect against influenza virus (IFV) infection in a murine model and that the protective effects might be mediated

by the augmentation of secreted immunoglobulin A production and the enhancement of innate immunity in the host (Yasui et al., 1999, 2004; Hori et al., 2002; Maeda et al., 2009; Kawase et al., 2010; Kobayashi et al., 2010). Influenza is an acute viral respiratory disease caused by IFV, which attacks the host respiratory tract mucosa. IFV infection sometimes causes lethal pneumonia in the elderly and encephalopathy in children, which results in high morbidity and significant mortality. After IFV infection in the lung, viruses are initially detected and destroyed nonspecifically by innate

immune responses, in which macrophages C59 wnt chemical structure and natural killer (NK) cells are involved, and if the viruses escape the early defense mechanisms, they are detected and eliminated specifically by adaptive immune responses (Tamura & Kurata, 2004). Following viral infection in the lung, alveolar macro-phages secrete various cytokines Non-specific serine/threonine protein kinase such as interleukin-12 (IL-12) that induce early NK cell-mediated interferon-γ (IFN-γ) production (Monteiro et al., 1998). The activated NK cells lyse virus-infected cells and contribute to the inhibition of early viral replication (Stein-Streilein & Guffee, 1986). In the adaptive immune response, secretory IgA and cytotoxic T lymphocytes specific for the viral antigen are induced and contribute to the recovery from viral infection (Wiley et al., 2001; Asahi et al., 2002). However, adaptive immunity requires several days for clonal expansion and the differentiation of naive lymphocytes into effector cells. Thus, as a method for preventing IFV infection, it would be crucial to enhance innate immunity that acts at the early stage of viral infection. Several studies have demonstrated that the strains of LAB that induce IL-12 elicit NK cell activities and IFN-γ production in an IL-12-dependent manner and enhance innate immunity (Ogawa et al., 2006; Shida et al., 2006a; Koizumi et al.