Innate immune defense mechanisms activated by pathogen recognition can be roughly divided into two categories: 1) those aimed at direct killing of the pathogen (microbicidal); 2) those aimed at the development of inflammation (pro-inflammatory). The final goal of both types of mechanisms is elimination of the pathogen and restoration of homeostasis. However, inflammation is accompanied by damage of self tissues, which often has a negative impact on the outcome of infection. Therefore, there is a need in such approaches to immunoprophylaxy and immunotherapy of infections that would enhance antimicrobial defense while minimizing inflammation. A key approach is elevation of epithelial barrier resistance. The proposed concept of immunostimulation is exemplified using COVID-19 infection.