Figure 1.

Immunosuppression tactics in the intermediate host. (A) Snails employ a wide variety of both humoral and cellular factors in combatting schistosome infections, many of which incorporate with each other to facilitate parasite killing. The humoral factors are largely composed of PRRs but also feature cytotoxic components such as biomphalysin. The cellular arm of the immune response features BgTLR displaying granulocytes, which envelope invading schistosomes, and hyalinocytes, which seemingly focus on the production of humoral factors and cell signaling molecules. (B) Parasites employ molecular mimicry by utilizing surface molecules and E/S products which share glycosylation patterns seen in snail plasma and on the surface of circulating hemocytes. Sharing such glycosylation patterns has been shown to correlate with survival during infection, suggesting these shared epitopes help schistosomes avoid recognition within the snail. (C) Molecular mimicry is also employed by the production of immune cell inactivating hormones like those produced by the snail which renders normally lethal hemocytes inactive and unable to kill invading sporocysts. (D) In order to avoid recognition by host pattern recognition receptors, schistosomes employ a highly variable series of polymorphic mucins. These mucins are recognized by host BgFREPs, and the variable nature of both the mucins and FREPs has led to the understanding that successful recognition of SmPoMucs by FREPs is a key determinant of infection success. If the host FREP can recognize the SmPoMucs and the surface of a sporocyst, that sporocyst will likely be killed, while having an unrecognizable SmPoMuc leads to immune evasion by avoiding BgFREP recognition. Such killing is thought to be at least partially dependent on a humoral BgFREP/BgTEP/Biomphalysin complex. (E) In order to generate a highly variable surface mucin, numerous processes occur to give rise to the considerable amount of variability seen between different sporocyst SmPoMucs. (F) Miracidia employ a venom allergen like protein which has been shown to upregulate the production of a B. glabrata matrix metalloproteinase (BgMMP1). This metalloproteinase is hypothesized to facilitate degradation of host connective tissues. Such degradation would allow for easier movement further into the host during initial infection. (G) E/S products from developing sporocysts facilitate the downregulation of key anti-parasitic functions in hemocytes. While some of these proteins have been identified, others remain of an unknown composition and are merely referred to by their size. (H) SmLeish-2 released by the parasite reduces hemocyte motility and therefore downregulates parasite encapsulation. This allows for continued movement and development of the sporocyst within the host.