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

Abstract

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 proinflammatory cytokines such as IL-6 and TNF-a 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-g, IL-2, IL-12 and IL-18. Even in non-infected mice, MM-2 administration also induced significant enhancement of both IFN-g 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.

Innate immune signaling and regulation in cancer immunotherapy

“…Gene expression profiling of these DCs revealed evidence for a modest pre-activation of DCs when Bifidobacterium was present, arguing for an innate immune mechanism for this improved immune activation effect [90]. This observation is similar to what has been reported in a viral infection model, in which gut bacteria induced APC "poising" [91]. In agreement, germ-free or antibiotic-treated mice, which completely lack or have a compromised commensal microbiota, showed defective innate immunity during viral infection [92,93].…”

Gut microbiota-mediated protection against influenza virus subtype H9N2 in chickens is associated with modulation of the innate responses

“…Recently, we showed that changes in the composition of the gut microbiota towards a dysbiotic condition resulted in higher oropharyngeal and cloacal shedding of AIV subtype H9N2 in chickens, which was also associated with compromised type I interferon (IFN) expression 19 . However, altering the composition of gut microbiota using probiotics has shown beneficial effects on immunity to influenza virus infection 20,21 . For instance, oral administration of a human isolate of Bifidobacterium longum MM-2 to influenza-infected mice reduced influenza virus associated mortality and inflammatory responses in the lower respiratory tract 20 .…”

“…However, altering the composition of gut microbiota using probiotics has shown beneficial effects on immunity to influenza virus infection 20,21 . For instance, oral administration of a human isolate of Bifidobacterium longum MM-2 to influenza-infected mice reduced influenza virus associated mortality and inflammatory responses in the lower respiratory tract 20 . The major mechanisms involved were shown to be the activation of natural killer (NK) cells both in the lungs and spleen and increased expression of various cytokines in the lungs 20 .…”

“…For instance, oral administration of a human isolate of Bifidobacterium longum MM-2 to influenza-infected mice reduced influenza virus associated mortality and inflammatory responses in the lower respiratory tract 20 . The major mechanisms involved were shown to be the activation of natural killer (NK) cells both in the lungs and spleen and increased expression of various cytokines in the lungs 20 . Furthermore, oral administration of heat-killed Lactobacillus plantarum L-137 to mice infected with influenza virus enhanced protection against the virus and reduced virus titre via a type I interferon dependent mechanism 21 .…”

Exploring the role of the microbiota member Bifidobacterium in modulating immune-linked diseases

“…Kawahara et al [65] reported that supplementation with B. longum MM-2 was linked to increases in natural killer (NK) cell activity, potentially via an increase in NK cell-activating cytokines such as IL-18, and correlated with anti-influenza virus responses. In an obesity-associated inflammation model, B. pseudocatenulatum CECT 7765 reduced B-cell (CD19 + ) and pro-inflammatory macrophages (F4/80 + CD11c − CD206 + ), as well as increasing Treg responses, which correlated with reduced body weight gain and improved glucose tolerance [66].…”