The extensive morbidity and mortality caused by influenza A viruses worldwide prompts the need for a
deeper understanding of the host immune response and novel therapeutic and/or prophylactic interventions.
In this study, we assessed the sublingual route as an effective means of delivering probiotics against
influenza virus in mice. In addition, IgA levels, NK cell activity, T cell activation, and cytokine profiles in
the lungs were examined to understand the mechanism underlying this protective effect. Sublingual
administration of Lactobacillus rhamnosus provided enhanced protection against influenza virus infection
by enhancing mucosal secretory IgA production, and T and NK cell activity. Moreover, interleukin (IL)-12
levels in the lungs increased significantly. Conversely, IL-6 and tumor necrosis factor alpha levels in the
lungs decreased significantly. On the basis of these promising findings, we propose that the sublingual
mucosal route is an attractive alternative to mucosal routes for administering probiotics against influenza
virus.