Using a 3D human in vitro staphylococcal pneumonia model, we show that α-toxin-induced activation of ADAM10 as well as α-toxin-induced cytotoxicity leads to increased CX3CL1 release, which enhances monocyte motility and impairs intracellular killing capacity by monocytes. Here, ADAM10 is linked to staphylococcal pneumonia.