Schistosomes are parasitic flatworms that infect the vasculature of >200 million people around the world. These long-lived parasites do not appear to provoke blood clot formation or obvious inflammation around them in vivo. Proteins expressed at the host–parasite interface (such as Schistosoma mansoni alkaline phosphatase, SmAP) are likely key to these abilities. SmAP is a glycoprotein that hydrolyses the artificial substrate p-nitrophenyl phosphate in a reaction that requires Mg2+ and at an optimal pH of 9. SmAP additionally cleaves the nucleoside monophosphates AMP, CMP, GMP, and TMP, all with a similar Km (~600–650 μM). Living adult worms, incubated in murine plasma for 1 h, alter the plasma metabolome; a decrease in sphingosine-1-phosphate (S1P) is accompanied by an increase in the levels of its component parts—sphingosine and phosphate. To test the hypothesis that schistosomes can hydrolyze S1P (and not merely recruit or activate a host plasma enzyme with this function), living intravascular life-stage parasites were incubated with commercially obtained S1P and cleavage of S1P was detected. Parasites whose SmAP gene was suppressed using RNAi were impaired in their ability to cleave S1P compared to controls. In addition, recombinant SmAP hydrolyzed S1P. Since extracellular S1P plays key roles in controlling inflammation and platelet aggregation, we hypothesize that schistosome SmAP, by degrading S1P, can regulate the level of this bioactive lipid in the environment of the parasites to control these processes in the worm’s local environment. This is the first report of any parasite being able to cleave S1P.

Schistosomes are intravascular parasitic platyhelminthes infecting > 200 million people globally and causing a debilitating disease, schistosomiasis. Despite the relatively large size of the adult worms and their disruption of blood flow, surprisingly, they do not appear to provoke thrombus formation around them in vivo. We hypothesize that proteins expressed at the host-parasite interface are key to this ability. Here, we functionally express an ectonucleotide pyrophosphatase/phosphodiesterase homologue, SmNPP5, that is expressed at the tegumental surface of intravascular . We report that SmNPP5, a known virulence factor for the worms, is a type one glycoprotein that cleaves the artificial substrate-Nph-5'-TMP in a reaction that requires cations and at an optimal pH of 9. Using immunolocalization and enzyme activity measurements, we confirm that SmNPP5 is exclusively expressed at the host interactive surface of all intravascular life stages. SmNPP5 inhibits platelet aggregation in a dose-dependent manner, as measured by multiple electrode aggregometry (MEA) using whole blood. Inhibition is apparent when either collagen or adenosine diphosphate (ADP) is used as agonist but is lost following heat treatment of SmNPP5. Unlike its mammalian homologue, NPP5, the schistosome protein cleaves ADP and with a Km of 246 ± 34 µM. In sum, SmNPP5 is expressed in the intravascular environment where it can degrade ADP and act as an anticoagulant. In this manner, the protein likely helps limit blood clot formation around the worms in vivo to permit the parasites free movement within the vasculature.

Airway epithelial cells, which lines the respiratory mucosa is in direct contact with the environment. Airway epithelial cells are the primary target for rhinovirus and other inhaled pathogens. In response to rhinovirus infection, airway epithelial cells mount both pro-inflammatory responses and antiviral innate immune responses to clear the virus efficiently. Some of the antiviral responses include the expression of IFNs, endoplasmic reticulum stress induced unfolded protein response and autophagy. Airway epithelial cells also recruits other innate immune cells to establish antiviral state and resolve the inflammation in the lungs. In patients with chronic lung disease, these responses may be either defective or induced in excess leading to deficient clearing of virus and sustained inflammation. In this review, we will discuss the mechanisms underlying antiviral innate immunity and the dysregulation of some of these mechanisms in patients with chronic lung diseases.