Trained immunity is a recent concept in the field of the innate immunity. Following a first challenge, the innate immune system adapts to show an enhanced response to a secondary homologous or heterologous challenge. This process involves metabolic, epigenetic, and functional reprogramming of innate immune cells. However, the persistence of the training remains incompletely identified. Here, using a mouse model, we tested whether training 9 weeks before challenge protected from bacterial infection, and 1 week and 6 months before challenge from viral infection. Mice were trained with zymosan (fungal cell wall preparation rich in β-glucan) and subjected to intravenous Listeria monocytogenes or intranasal H1N1 challenge. Morbidity and mortality, as well as bacteremia, in vivo bioluminescence, histological analyses of liver and lungs, cellular metabolism and functions of monocytes and PMNs were collected.
Nine weeks following training, mice showed improved immune response against Listeria monocytogenes. PMNs from trained mice display enhanced functions and energetic metabolism and monocytes from trained mice display enhanced energetic metabolism. One week following training, trained mice showed higher vulnerability to H1N1 infection, PMNs and monocytes showed enhanced energetic metabolism and monocytes showed enhanced functions. Six months following training, we did not detect signs of persistence of training.
Overall, data presented here show that training protects from Listeria monocytogenes infection up to 9 weeks following training induction. Furthermore, 1 week following training, effects of H1N1 infection remain to be clarified, and persistence or resolution of training after 6 months remains to be established.