Macrophages produce a soluble mediator which enables neutrophils to kill the parasitic nematode Strongyloides stercoralis (51.4)

Abstract

Abstract Neutrophil recruitment to the parasite microenvironment via CXCR2 is required for killing of Strongyloides stercoralis infective larvae during the primary and secondary immune responses. Neutrophils isolated from other cell types within diffusion chambers are capable of killing L3 in vivo, however, isolated neutrophils are unable to kill larvae in vitro. Macrophages have been shown to be required for in vivo killing of other nematode species. We hypothesized that neutrophils require soluble mediators that can be supplied by macrophages in vivo, explaining their inability to kill in isolation in vitro. Combining neutrophils with macrophages at a 4:1 ratio in vitro led to a robust larvicidal response, while neither cell type was able to facilitate larval killing independently. The killing response occurred whether naïve or immune mouse serum was used, which suggests that neutrophil-macrophage cooperation is a component of the primary immune response. Furthermore, the killing process was complement-dependent, as killing was ablated when serum from C3−/− mice was used. Combining cell free supernatant from cultured macrophages with neutrophils also led to larval killing, indicating that the cooperation between neutrophils and macrophages is dependent on a soluble factor from macrophages inducing larval killing by neutrophils.