There is a growing appreciation that macrophages contribute to innate immune memory against microbial pathogens in ways that are distinct from and complementary to adaptive immune memory. In PNAS, Chan et al. (1) report that macrophages develop memory against Staphylococcus aureus skin and skin structure infections (SSSIs) and that this memory is tissue specific and can be transferred between individual animals.
Immune memory against S. aureus is important because of the immense impact of this microbe on human health and because effective immunity against recurrent S. aureus infections can be difficult to achieve. S. aureus is the most common cause of skin infections (2). These are often associated with massive morbidity, mortality, and health care expenditures (3). Patients often experience high rates of recurrence (4), suggesting that some individuals have difficulty with establishing protective immunity against this organism. Humoral immunity in particular can often be ineffective because antibodies directed against S. aureus virulence factors may not be sufficient for protection (5). Consistent with this, individuals with impaired humoral immunity are not necessarily at increased risk for S. aureus infections (6), and an effective vaccine against S. aureus has thus far proved elusive (7). Memory T cell responses, while robust, can likewise be ineffectual (8). These data suggest that adaptive immunity alone is unlikely to provide effective protection against S. aureus infection.
Studies of individuals with recurrent S. aureus infections in the context of a primary immunodeficiency have revealed critical roles for select cell types and immune mechanisms in protection against this potential pathogen. These include defects in IL-17 production associated with hyper-IgE syndrome (Job’s disease) (9). IL-17 was likewise shown in mouse models of S. aureus infection to be critical for neutrophil recruitment, abscess formation, and bacterial clearance (10 …
↵1To whom correspondence should be addressed. Email: pbollyky{at}stanford.edu.
