Infectious and lifestyle modifiers of immunity and host resilience

The interindividual heterogeneity of the immune system likely determines the personal risk for acquiring infections and developing diseases with inflammatory components. In addition to genetic factors, the immune system’s heterogeneity is driven by diverging exposures of leukocytes and their progenitors to infections, vaccinations, and health behavior, including lifestyle-related stimuli such as diet, physical inactivity, and psychosocial stress. We review how such experiences alter immune cell responses to concurrent and subsequent challenges, leading to either improved host resilience or disease susceptibility due to a muted or overzealous immune system, with a primary focus on the contribution of innate immune cells. We explore the involvement of diverse mechanisms, including trained immunity, and their relevance for infections and cardiovascular disease, as these prevalent conditions are heavily influenced by immune cell abundance and phenotypic adaptions. Understanding the mechanistic bases of immune modulations by prior or co-exposures may lead to new therapies targeting dysfunctional inflammation.