Interleukin-33 facilitates cutaneous defense against Staphylococcus aureus by promoting the development of neutrophil extracellular trap.

Neutrophil extracellular traps (NETs) are consisted of DNA fibers and granular proteins and the formation of NETs has been identified as a crucial element of innate immune defense. IL-33 is a member of the IL-1 family cytokines and has been known as a strong trigger of type-2 immunity. Growing studies imply that IL-33 is involved in host defense against microbial infection. Here, we investigate the underlying influence of IL-33 on NET formation in mice with S. aureus cutaneous infection. We found that the level of IL-33 was significantly elevated in skin lesions of S. aureus-infected mice. The alarmin IL-33 inspired host innate defense through activation of NADPH oxidase to produce reactive oxygen species (ROS). Besides mediating the direct bactericidal activity within phagolysosomes, ROS production in IL-33-primed neutrophils was also critical for induction of NET formation. Enhancement of NET production by IL-33 contributed to ensnaring S. aureus and bacterial killing activity in vitro and in vivo. All together, these findings set up an IL-33/ST2 axis modulating NET generation, which strengthens host defense of innate immunity against S. aureus infection.