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Motile invaded neutrophils in the small intestine of Toxoplasma gondii-infected mice reveal a potential mechanism for parasite spread

Significance Toxoplasma gondii infection occurs following consumption of infected meat or contaminated water and produce. As a result, the parasite first enters the body in the intestine, but we understand surprisingly little about how it behaves there. In this study, we show that T. gondii can invade neutrophils in the intestine directly, hitching a ride in these cells as they migrate out of the intestinal tissue into the lumen. Our findings implicate neutrophils and other immune cells in a surprising luminal pathway for the spread of infection and suggest new targets for therapeutic intervention in oral infection. Toxoplasma gondii infection occurs through the oral route, but we lack important information about how the parasite interacts with the host immune system in the intestine. We used two-photon laser-scanning microscopy in conjunction with a mouse model of oral T. gondii infection to address this issue. T. gondii established discrete foci of infection in the small intestine, eliciting the recruitment and transepithelial migration of neutrophils and inflammatory monocytes. Neutrophils accounted for a high proportion of actively invaded cells, and we provide evidence for a role for transmigrating neutrophils and other immune cells in the spread of T. gondii infection through the lumen of the intestine. Our data identify neutrophils as motile reservoirs of T. gondii infection and suggest a surprising retrograde pathway for parasite spread in the intestine.