Résumé
The parasite Cryptosporidium invades and replicates in intestinal epithelial cells and is a leading cause of diarrheal disease and early childhood mortality. The molecular mechanisms that underlie infection and pathogenesis are largely unknown. Here, we delineate the events of host cell invasion and uncover a mechanism unique to Cryptosporidium. We developed a screen to identify parasite effectors, finding the injection of multiple parasite proteins into the host from the rhoptry organelle. These factors are targeted to diverse locations within the host cell and its interface with the parasite. One identified effector, rhoptry protein 1 (ROP1), accumulates in the terminal web of enterocytes through direct interaction with the host protein LIM domain only 7 (LMO7) an organizer of epithelial cell polarity and cell-cell adhesion. Genetic ablation of LMO7 or ROP1 in mice or parasites, respectively, impacts parasite burden in vivo in opposite ways. Taken together, these data provide molecular insight into how Cryptosporidium manipulates its intestinal host niche.
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•Live imaging of Cryptosporidium invasion shows host actin and membrane modification•Screen identifies and validates the first 6 Cryptosporidium rhoptry bulb proteins•ROP1 is injected into the host cell and binds LMO7, a host cytoskeletal modulator•Genetic ablation of ROP1 or LMO7 impacts on parasite infection in vivo
The parasite Cryptosporidium infects enterocytes and causes severe diarrheal disease. Guérin et al. used live imaging to unravel the mechanism of parasite invasion and discover proteins secreted in this process that modify the host cell. Identifying such molecular interactions between parasite and host is key to understand and combat infection.