From the levels of lymphocyte subsets (CD4+, CD8+), the expression of cytokines (TNF-α, IL1β, IL-10, and IFN-γ), observation of pathological changes in organs (heart, liver, spleen, kidney, and brain), and the bacterial load of the spleen, we concluded the therapeutic effect of LP8 against listeriosis and demonstrate the feasibility of a combined therapy to reduce the use of antibiotics. This evidence concerns the gene CD4 and listeriosis.