Defense mechanisms protecting the lungs against infection involve a defensive layer of epithelial cells. Disruption of the integrity of this barrier, resulting from chronic pulmonary diseases, allows pathogens such as Staphylococcus aureus to contribute to the development of severe pneumonia. Beyond innate and adaptive immune responses, innate immune memory, or trained immunity (TI), was recently defined as one form of adaptation of innate host defense that is characterized by the host's ability to generate a robust and lasting immune response to subsequent unrelated challenges, induced by prior stimulation through epigenetic and metabolic reprogramming after the first stimulation. The knowledge about non-immune cells, which possess immunological memory, is scarce. An opportunistic pathogen, S. aureus, is responsible for the multitude of human diseases, including pneumonia, endocarditis and osteomyelitis, or animals, such as chronic cattle mastitis that is extremely difficult to treat. An induction of trained immunity may be considered as a therapeutic alternative during S. aureus infection.