Neutrophils and macrophages in the immune response to parasitic helminths
Neutrophils and macrophages are complex components of the immune system, functioning both as effector killing cells and as initiators and modulators of the development of protective immunity. It was hypothesized that the function and regulation of neutrophils and macrophages is tightly coupled to the ability to defend against parasitic helminths. Using a mouse model of nematode infection, it is determined that neutrophil recruitment to Strongyloides stercoralis occurs directly in response to parasite extract in a manner that is dependent on CXCR2. IL-17R signaling was required neither for neutrophil recruitment nor for the development of host immunity in this model. The ability of neutrophils to kill S. stercoralis was found to be dependent on myeloperoxidase, and mice deficient in myeloperoxidase were unable to mount effective primary or secondary immune responses. Furthermore, the larvicidal activity of neutrophils against S. stercoralis was not an involuntary response, as naïve neutrophils were unable to precipitate larval death in vitro unless macrophages were also in the larval microenvironment. Macrophage regulation was also shown to be important in a model of cestode infection, as IL-4-/- mice succumbed to Mesocestoides corti infection, having decreased numbers of macrophages at the site of infection and decreased expression of alternatively activated macrophage markers. In both of these helminth infection models, host immunity was shown to be dependent on the development of neutrophil and macrophage populations at the site of infection and on the apposite functioning of these cells. In conclusion, the appropriate activity and regulation of neutrophils and macrophages is an important determinant of immunity to helminth parasites.