A central role in the innate immune response and protection against staphylococcal infection is played by the central molecule of complement C3 but not factor B. In fact, mice with C3 deficiency show susceptibility to S. aureus septic arthritis and display impaired host clearance, presumably due to reduced opsonization and phagocytosis of bacteria (Na et al., 2016). Here, C3 is linked to bacterial arthritis.