Plasma levels of innate immune mediators are associated with liver fibrosis in low parasite burden Schistosoma mansoni‐infected individuals

Abstract

In the murine model, it was demonstrated that pro-inflammatory cytokines and chemokines are essential to the formation and modulation of Schistosoma-induced granulomatous inflammation. However, the relationship of these immune mediators and disease severity is hard to be established in naturally infected individuals. The current study evaluates the association between plasma concentrations of MIF, sTNF-R1, CCL3, CCL7 and CCL24 and schistosomiasis morbidity in Schistosoma mansoni-infected patients with a low parasite burden. For this propose, 97 S. mansoni-infected individuals were subjected to abdominal ultrasound analysis and clinical examination. Among them, 88 had plasma concentration of immune mediators estimated by ELISA assay. Multivariate linear regression models were used to evaluate the relationship between the plasma concentration of immune mediators and the variables investigated. Although most individuals presented low parasite burden, over 30% of them showed signs of fibrosis defined by ultrasound measurements and 2 patients had a severe form of schistosomiasis. No association between parasite burden and the plasma levels of chemokine/cytokines or disease severity was observed. There was a positive association between plasma concentration of CCL4, sTNF-R1, CCL3 and MIF with gall bladder thickness and/or with portal vein thickness that are liver fibrosis markers. In contrast, no association was found between CCL7 plasma concentrations with any of the schistosomiasis morbidity parameters evaluated. The data showed that CCL24, sTNFR1, MIF and CCL3 can be detected in plasma of S. mansoni-infected individuals and their concentration would be used as prognostic makers of Schistosoma-induced liver fibrosis, even in individuals with low parasite burden.

Effect of maternal praziquantel treatment for Schistosoma japonicum infection on the offspring susceptibility and immunologic response to infection at age six, a cohort study

“…Turning to the influence of infection on immune responses, serum TNF-RI was significantly higher among cases of S. japonicum compared to children who were uninfected. Similar results were reported in the context of S. mansoni [37]. TNF-RI is a receptor for the proinflammatory cytokine TNF-α, which is associated with chronic human schistosomiasis and contributes to granuloma formation [38][39][40][41].…”

Host Regulators of Liver Fibrosis During Human Schistosomiasis

“…This observation was corroborated by independent data obtained from murine models which reported a less severe granulomatous response in CCL3-deficient mice following schistosome infection ( 56 , 90 ). The findings were further confirmed in another study where the plasma concentrations of CCL3 and that of other chemokines, namely CCL24, sTNFR1 and MIF (migration inhibitory Factor), were associated with hepatic fibrosis progression ( 57 ).…”

Sex-Specific Modulation of the Host Transcriptome in the Spleen of Schistosoma mansoni-Infected Mice

“…Chemokine (C-C motif) ligand 24 is a small cytokine chemotactic for eosinophils, resting T lymphocytes and neutrophils ( Patel et al., 1997 ; White et al., 1997 ). The plasma concentration of CCL24 was shown to be significantly higher in S. mansoni -infected individuals than in non-infected individuals ( Rodrigues Oliveira et al., 2018 ). Higher expression of CCL24 is one more indicator of the stimulation of the host immune system by male worms.…”