Clearance of intestinal helminth infection and acquired resistance is dependent on an appropriate type-2 immune response. In the Trichuris muris (Tm) infection model in mice, resistant strains expel worms via a Th2 cell-mediated response whereas susceptible strains produce high levels of Th1 cell-associated cytokines and become chronically infected. Myeloid-cell specific deletion of Ship1 (SHIPΔLysM) in a normally resistant mouse strain (C57Bl6) results in chronic infection because of inappropriate production of IL12 in the intestine and mesenteric lymph nodes (mLNs) in Tm-infected mice. Although Ship1-deficient macrophages overproduce IL12 in vitro and in vivo and thus likely contribute to the Tm-susceptibility of SHIPΔLysM mice; surprisingly, deletion of Ship1 in the neutrophil lineage alone (SHIPΔPMN) is sufficient to render a resistant strain susceptible. Chronic worm burden in SHIPΔPMN mice is associated with elevated IL12, IFNγ and decreased IL13 production in the intestine and mLNs. These data suggest that regulation of neutrophil function by Ship1 is required for parasite clearance in response to Tm infection. Although neutrophils are rapidly recruited to the intestine following Tm infection, neutrophils are not required for clearance of parasites. However, our results suggest that dysregulated neutrophil activity can contribute to chronic parasitic infection.
- Copyright © 2013 by The American Association of Immunologists, Inc.