Novel mechanisms of conferring broad protection against influenza by Lactobacillus casei lactic acid bacteria by mobilizing innate and adaptive immune cells (INC1P.354)

Heat-killed Lactobacillus casei strain lactic acid bacteria DK128 was investigated as potential probiotics to determine its antiviral effects on influenza virus. Intranasal pretreatment of mice with heat-killed DK128 resulted in the recruitment of various innate immune cells into the airways, conferring broad protection against lethal infection with H1, H3, and H5 subtype influenza viruses, preventing body weight loss, and lowering lung viral loads. The protection against lethal infection as a result of killed-DK128 pretreatment was correlated with significantly reduced infiltrates of natural killer cells, neutrophils, and monocytes as well as with increased alveolar macrophage populations. Mice with killed-DK128-mediated protection against H3N2 primary infection effectively developed heterosubtypic adaptive immunity to H1N1 pandemic virus. Further mechanistic studies using various knockout mouse models discovered that B cells but not CD4 and CD8 T cells were absolutely required for heat-killed DK128-mediated protection. Therefore, this study provides evidence that heat-killed DK128 can be developed as beneficial probiotics and that the cross-talk between innate and adaptive immune cells is playing an essential role in conferring influenza antiviral immunity.