Human Schistosomiasis Is Associated with Endotoxemia and Toll-Like Receptor 2- and 4-Bearing B Cells

Abstract

Schistosomiasis is caused by parasitic trematodes. Individuals can accumulate hundreds of intravascular worms, which secrete a myriad of antigenic molecules into the bloodstream. Some of these molecules suppress immunity to microbial Toll-like receptor (TLR) ligands, such as lipopolysaccharides, which may increase host susceptibility to coinfecting pathogens. We show that schistosomiasis is associated with extremely high levels of endotoxemia as well as high mobility group 1, an endogenous inflammatory TLR ligand, in the absence of other coinfected pathogens. Circulating B cells express surface TLR2 and TLR4, reflecting systemic exposure to microbial ligands. Bacterial translocation may occur with schistosomal egg movement from the vascular to the gut and other routes, such as the skin during infection. Our report suggests that immunosuppressive schistosome antigens may have evolved to curb inflammatory responses to the high antigenic burden of translocated bacteria products and endogenous TLR ligands that arise during parasite exposure and inflammation.

Fasciola hepaticaFatty Acid Binding Protein Inhibits TLR4 Activation and Suppresses the Inflammatory Cytokines Induced by Lipopolysaccharide In Vitro and In Vivo

“…Indeed, septicemia is not a common event during helminth infection (53), which supports the therapeutic potential of helminth antigens. Using specific helminth molecules to target innate immune cell signaling will circumvent the problem of global immune suppression associated with parasite infection and also with current immune-therapies.…”

Reduced Frequency of a CD14+CD16+Monocyte Subset with High Toll-Like Receptor 4 Expression in Cord Blood Compared to Adult Blood Contributes to Lipopolysaccharide Hyporesponsiveness in Newborns

“…This concept is supported by observations that offspring of mothers with chronic intravascular parasitic infections, such as malaria, schistosomiasis, and lymphatic filariasis, and whose fetal lymphocytes acquired antigen-specific recall responses to soluble antigens from these parasites (a potential marker for prenatal exposure to proinflammatory mediators), developed enhanced LPS responsiveness and expanded populations of CD14 ϩ CD16 ϩ monocytes. Malaria is a potent inducer of TNF-␣ (42), and chronic schistosomiasis results in elevation of plasma endotoxin (43).…”

Maternal schistosomiasis: a growing concern in sub-Saharan Africa

“…63,64 A recent study among Philippine pregnant women has also implicated schistosomiasis in elevated maternal and placental compartment endotoxin levels. 65 Microbial translocation due to schistosome egg-induced pathology in the gut has been reported as the cause of increase in plasma levels of lipopolysaccharide endotoxin, 66 which has also been shown to induce an anemic condition. 67 It is evident from all of these studies that schistosomiasis-induced morbidity during pregnancy is complex, employing both direct and indirect routes in the pathogenesis (Fig.…”