Osteopontin Is Upregulated in Human and Murine Acute Schistosomiasis Mansoni

Abstract

BackgroundSymptomatic acute schistosomiasis mansoni is a systemic hypersensitivity reaction against the migrating schistosomula and mature eggs after a primary infection. The mechanisms involved in the pathogenesis of acute schistosomiasis are not fully elucidated. Osteopontin has been implicated in granulomatous reactions and in acute hepatic injury. Our aims were to evaluate if osteopontin plays a role in acute Schistosoma mansoni infection in both human and experimentally infected mice and if circulating OPN levels could be a novel biomarker of this infection.Methodology/Principal FindingsSerum/plasma osteopontin levels were measured by ELISA in patients with acute (n = 28), hepatointestinal (n = 26), hepatosplenic (n = 39) schistosomiasis and in uninfected controls (n = 21). Liver osteopontin was assessed by immunohistochemistry in needle biopsies of 5 patients. Sera and hepatic osteopontin were quantified in the murine model of schistosomiasis mansoni during acute (7 and 8 weeks post infection, n = 10) and chronic (30 weeks post infection, n = 8) phase. Circulating osteopontin levels are increased in patients with acute schistosomiasis (p = 0.0001). The highest levels of OPN were observed during the peak of clinical symptoms (7–11 weeks post infection), returning to baseline level once the granulomas were modulated (>12 weeks post infection). The plasma levels in acute schistosomiasis were even higher than in hepatosplenic patients. The murine model mirrored the human disease. Macrophages were the major source of OPN in human and murine acute schistosomiasis, while the ductular reaction maintains OPN production in hepatosplenic disease. Soluble egg antigens from S. mansoni induced OPN expression in primary human kupffer cells.Conclusions/SignificanceS. mansoni egg antigens induce the production of OPN by macrophages in the necrotic-exudative granulomas characteristic of acute schistosomiasis mansoni. Circulating OPN levels are upregulated in human and murine acute schistosomiasis and could be a non-invasive biomarker of this form of disease.

Osteopontin and malaria: no direct effect on parasite growth, but correlation with P. falciparum-specific B cells and BAFF in a malaria endemic area

“…Such a discrepancy in results between studies could be due to the use of OPN ELISA kits from different manufacturers, or because of different ethnicities in the study populations. Studies using ELISA kits from the same manufacturer as in this study present OPN plasma concentrations in healthy adults similar to ours [ 49 , 51 , 52 ]. Additionally, we included a small set of Swedish samples, and these results indicate that there is no difference in OPN concentration depending on ethnicity/country of residence or sex, but the cohort was small and not aged-matched, hence the results must be interpreted with caution.…”

Host Regulators of Liver Fibrosis During Human Schistosomiasis

“…In fact, Syn et al elegantly demonstrated that the pro-fibrogenic effects induced by the Hedgehog pathway are mediated by a secreted host phosphoprotein, osteopontin ( 93 ). This is substantiated by the observation that high osteopontin level in serum and liver tissue correlates with hepatic fibrosis during schistosome infection ( 65 , 66 ). This correlation was further validated in mechanistic chronic murine schistosomiasis model where higher levels of osteopontin release by macrophages associated with hepatosplenic disease ( 65 , 66 ).…”

“…This is substantiated by the observation that high osteopontin level in serum and liver tissue correlates with hepatic fibrosis during schistosome infection ( 65 , 66 ). This correlation was further validated in mechanistic chronic murine schistosomiasis model where higher levels of osteopontin release by macrophages associated with hepatosplenic disease ( 65 , 66 ). Fundamentally, these findings are consistent with the demonstrated role of osteopontin in inflammation, immunity, angiogenesis, fibrogenesis and carcinogenesis in various tissues ( 94 ).…”

Diagnosis of schistosomiasis mansoni: an evaluation of existing methods and research towards single worm pair detection

“…Most reports have been concerned with the detection of host markers in the blood stream as an indicator of tissue damage caused by eggs (e.g. Pereira et al 2016). The CAA and CCA glycoproteins were the first secretome products identified and then developed for diagnostic puroposes.…”