Blood flukes exploit Peyer's Patch lymphoid tissue to facilitate transmission from the mammalian host

Schistosomes are blood-dwelling parasitic helminths which produce eggs in order to facilitate transmission. Intestinal schistosomes lay eggs in the mesenteries, however, it is unclear how their eggs escape the vasculature to exit the host. Using a murine model of infection, we reveal that Schistosoma mansoni exploits Peyer's Patches (PP) gut lymphoid tissue as a preferential route of egress for their eggs. Egg deposition is favoured within PP as a result of their more abundant vasculature. Moreover, the presence of eggs causes significant vascular remodeling leading to an expanded venule network. Egg deposition results in a decrease in stromal integrity and lymphoid cellularity, including secretory IgA producing lymphocytes, and the focal recruitment of macrophages. In mice lacking PP, egg excretion is significantly impaired, leading to greater numbers of ova being entrapped in tissues and consequently, exacerbated morbidity. Thus, we demonstrate how schistosomes directly facilitate transmission from the host by targeting lymphoid tissue. For the host, PP-dependency of egg egress represents a trade-off, as limiting potentially life-threatening morbidity is balanced by loss of PP structure and perturbed PP IgA production.
Author Summary Schistosomes are parasitic helminths that parasitise >200 million people worldwide. Adult worm pairs of intestinal schistosomes lay their eggs in the mesenteric veins from which the eggs need to pass into the lumen prior to excretion and completion of their life cycle. However, it is not known how eggs transfer from the intestinal vasculature to reach the gut lumen. Here, we reveal using a mouse model of infection, that Schistosoma mansoni exploits Peyer's Patches (PP) lymphoid tissues in the wall of the small intestine as a preferential route of egg egress. The eggs cause vascular remodelling in the PP leading to an expanded venule network, reduced stromal integrity, and decreased lymphoid cellularity. Most significantly, in mice rendered deficient in PP, egg excretion is impaired (despite intact immune responses), leading to greater numbers of eggs entrapped in tissues, and consequently exacerbated host morbidity. Thus, we demonstrate how schistosomes directly facilitate transmission from the host by targeting lymphoid tissue. For the host, this represents a trade-off as limiting life-threatening morbidity is balanced by loss of PP structure and function. The requirement of PP for efficient schistosome egress may be a significant risk factor of developing severe disease within heavily infected human populations.