The esophageal gland mediates host immune evasion by the human parasiteSchistosoma mansoni

Abstract

Schistosomes are parasitic flatworms that cause schistosomiasis, a neglected tropical disease affecting over 200 million people. Schistosomes develop multiple body plans while navigating their complex life cycle, which involves two different hosts: a mammalian definitive host and a molluscan intermediate host. Their survival and propagation depend upon proliferation and differentiation of stem cells necessary for parasite homeostasis and reproduction. Infective larvae released from snails carry a handful of stem cells that serve as the likely source of new tissues as the parasite adapts to life inside the mammalian host; however, the role of these stem cells during this critical life cycle stage remains unclear. Here, we characterize stem cell fates during early intramammalian development. Surprisingly, we find that the esophageal gland, an accessory organ of the digestive tract, develops before the rest of the digestive system is formed and blood feeding is initiated, suggesting a role in processes beyond nutrient uptake. To explore such a role, we examine schistosomes that lack the esophageal gland due to knockdown of a forkhead-box transcription factor, Sm-foxA, which blocks development and maintenance of the esophageal gland, without affecting the development of other somatic tissues. Intriguingly, schistosomes lacking the esophageal gland die after transplantation into naive mice, but survive in immunodeficient mice lacking B cells. We show that parasites lacking the esophageal gland are unable to lyse ingested immune cells within the esophagus before passing them into the gut. These results unveil an immune-evasion mechanism mediated by the esophageal gland, which is essential for schistosome survival and pathogenesis.

Single-cell atlas of the first intra-mammalian developmental stage of the human parasite Schistosoma mansoni

“…3f and 6c, d ). The oesophageal gland is an anterior accessory organ of the digestive tract 60 and is crucial for degradation of host immune cells and parasite survival 61 . This group of cells also expressed other meg genes with high specificity such as meg8 (Smp_172180), meg9 (Smp_125320), meg11 (Smp_176020), meg15 (Smp_010550) and meg32.1 (Smp_132100) (Fig.…”

“…We also show through the FISH validation some level of co-localisation of tegumental genes with meg4 + oesophageal gland. Oesophagus connects the mouth to the gut and is surrounded by a gland that secretes, amongst other things, proteins encoded by meg genes that help process the ingested blood 63 , 88 by degrading immune cells and preventing them from entering the gut 61 . They are therefore crucial for parasitic development and a prime target for vaccine development 63 .…”

“…For schistosomula FISH, single FISH was initially performed for each gene and consistency in expression was determined across 5–10 worms. Following single FISH, multiple double FISH experiments were performed with various marker combinations, unless the marker has previously been extensively used in other studies (e.g., histone h2b (Smp_108390) 6 , 47 , 61 , meg-4 (Smp_307220) 6 , 59 , 61 , cathepsin B (Smp_103610) 6 , 47 , 61 , 66 , tsp-2 (Smp_335630) 6 , 7 , 61 ). Consistency in expression patterns was determined between 5–10 worms within the experiment, and also across different experiments including single FISH.…”

Innovations and Advances in Schistosome Stem Cell Research

“…Upon release by snails into fresh water, mature schistosome cercariae swim until they encounter a mammalian host, which they enter by transdermal penetration. During early intra-mammalian development, schistosome stem cells play vital roles in producing the tegument and the esophageal gland, an accessory digestive organ, which develops before the rest of the digestive system is formed ( 25 ). Differentiation driven by stem cells is faster than that which occurs in adults, and this results in the rapid growth and development of juvenile parasites ( 25 ).…”

Schistosoma mansoni alter transcription of immunomodulatory gene products following in vivo praziquantel exposure

“…These gene products are proposed to protect the parasite from ingested immune components and enzymes found in leukocytes and erythrocytes [33,53]. The schistosome esophagus is also a secretory organ, and it has been speculated that these secretions play a role in parasite immune-evasion [54][55][56][57]. PZQ-evoked up-regulation of esophageal transcripts (ex.…”