<i>Schistosoma mansoni</i> Soluble Egg Antigens Trigger Erythrocyte Cell Death

Abstract

Estimated to affect nearly 300 million people worldwide, schistosomiasis is caused by parasitic flatworms of the genus Schistosoma. The major pathological consequences of chronic schistosomiasis are associated with soluble egg antigens (SEA) secreted from schistosome egg deposits in liver and other organs. The vigorous immune responses induced by egg antigens result in granuloma formation and other pathophysiological symptoms such as hepatosplenomegaly and anemia. Risk of anemia correlates with infection intensity and the level of host hemoglobin is inversely proportional to egg count. Schistosomiasis-associated anemia could be multifactorial, but the potential link and molecular underpinnings are unclear. Here, we evaluate whether S. mansoni SEA affects survival of mouse erythrocytes. Erythrocytes incubated with different concentrations of SEA were tested for various markers of erythrocyte cell death. Erythrocytes exposed to SEA exhibit elevated intracellular Ca²⁺ levels as measured by Fluo-3 AM fluorescence in flow cytometry, and they also display concentration-dependent, Ca²⁺-dependent, and heat-sensitive increases in phosphatidyl serine exposure. Further, SEA-exposed erythrocytes show increased fluorescence using the in situ apoptosis marker CaspACE FITC, indicating the involvement of caspase-mediated cell deformation. Taken together, these results offer several lines of experimental evidence for SEA-induced erythrocyte cell death and may provide new insights into factors contributing to schistosomiasis-associated anemia.

Antigens of worms and eggs showed a differentiated detection of specific IgG according to the time of Schistosoma mansoni infection in mice

“…During schistosomiasis progression, schistosomes mature to adults in the hepatic circulation and then in pairs migrate to inhabit in the mesenteric veins, where they mate and lay a large number of eggs in the vessels of the intestinal wall 5 and other tissues, mainly in the liver. The major pathological consequences of chronic schistosomiasis are associated with soluble egg antigens secreted from schistosome egg that produces a vigorous inflammatory response resulting in granuloma formation 6 .…”

Expression of Fas (CD95) and Bcl-2 in peripheral blood mononuclear cells in patients with chronic HCV and schistosomiasis

“…It is well-established that cells obtained from patients with chronic infection fail to respond to antigens derived from S. mansoni [14]. Several lines of evidence suggest that antigens of S. mansoni can induce apoptosis of host T cells [15].…”

Apoptosis of non-parasitised red blood cells in Plasmodium yoelii malaria

“…This finding, together with the previous identification of nRBCs as target cells for the incorporation of plasmodial molecules ( Layez et al 2005 , Omodeo-Sale et al 2005 , Bratting et al 2008 ), suggested that malarial antigens could also have apoptogenic effects on nRBCs. In fact, it has previously been shown that nRBCs undergo erythrocytic apoptosis in P. falciparum culture in vitro ( Koka et al 2007 , Pattanapanyasat et al 2010 ), similar to RBCs following treatment with bacterial toxins and Schistosoma mansoni antigens in vitro ( Lang et al 2004 , Föller et al 2007 , Kasinathan & Greenberg 2010 ). Thus, in addition to the pathogenic effects of hyperparasitaemia mediated through the lysis and cytoadherence of pRBCs ( Lamikanra et al 2007 ), parasite load could induce nRBC apoptosis through a massive adsorption of parasitic antigens on nRBC membranes.…”

“…These factors include endogenous stimuli present in parasitic infections, such as anti-RBC antibodies, oxidative stress, nitric oxide (NO) and microbial antigens ( Mandal et al 2005 , Attanasio et al. 2007 , Nicolay et al 2008 , Kasinathan & Greenberg 2010 ). Thus, in the present study, we attempted to investigate the association of nRBC apoptosis with total RBC counts, parasite load, cytokines, NO and anti-RBC antibodies during the early and late stages of anaemia in experimentally infected P. yoelii 17XL BALB/c mice.…”