Cytokine profile, proliferation and phosphorylation of ERK1/2 and Akt in circulating mononuclear cells from individuals during the chronic intestinal phase of Schistosomiasis mansoni infection

Abstract

BackgroundThe immune response to Schistosoma mansoni is characterized by a granulomatous reaction around the parasite eggs that are trapped in the host liver, and this reaction modulates the immune response during the chronic phase of the disease. The typical peripheral blood mononuclear cell (PBMC) response of patients during the chronic intestinal phase of infection is characterized by a decreased response to an S. mansoni soluble egg antigen. To obtain a greater understanding of Schistosoma infections, this study investigated the effects of the soluble egg antigen (SEA) and soluble adult worm antigen (SWAP) of S. mansoni on cellular proliferation, cytokine production, and ERK1/2 and Akt phosphorylation in PBMCs from infected (XTO) and egg-negative (NI) individuals living in the same endemic area.MethodsThe activation status was evaluated by cell immunophenotypic staining (cytometry). The cell proliferation assay was by CFSE method. Cytokine detection assay (Th1 and Th2) was by Cytometric Bead and Array phosphorylation status was by ELISA.ResultsThe XTO, NI and BD (blood donor) individuals from an area not endemic for schistosomiasis were compared. The CD4+ T lymphocyte proliferation rate was lower in the XTO group, but not the NI group, after SEA stimulation compared to the BD group. The CD8+ T cell proliferation rate was lower in the XTO group in the unstimulated cultures and after both SEA and SWAP stimulation compared to the BD group. Cytokine analysis after either SEA or SWAP stimulation showed a balanced cytokine pattern in the XTO and NI groups. ERK1/2 and Akt phosphorylation were only marginally detected in all groups; however, a decrease in ERK 1/2 phosphorylation was observed in the SWAP-stimulated XTO group compared to both the NI and BD groups.ConclusionsThe data indicate that SEA-stimulated CD4+ T cells from infected patients have a lower proliferation rate than the same cells from the NI group. Furthermore, we observed that SWAP stimulation influences ERK1/2 phosphorylation in the XTO group.

Receptor Antagonist of IL‐13 Exerts a Potential Negative Regulation During Early Infection of Human Schistosomiasis

“…High levels of IL‐10 in patients infected with chronic forms of the disease have been demonstrated. This may be an attempt to control the immune modulation during schistosome infection, which would be essential for promoting the survival of patients . IL‐10 cytokine plays an important function in regulating the development of schistosomiasis in response to the cytokine production profiles of Th1 and Th2, and this is in accordance with the correlations found in our study.…”

“…Moreover, studies have demonstrated the function of Th1 cytokines in reducing hepatic fibrogenesis. Using our results, we identified an increase in IFN‐γ, IL‐2 and TNF‐α after antigenic stimulation (compared to when there was no stimulation) in patients with all patterns of fibrosis, which suggests the involvement of these cytokines in the reduction of PPF in chronically infected schistosomiasis patients .…”

“…In our studies, we identified a significant negative and positive correlation between IL‐13 and IFN‐γ in patients without fibrosis – A pattern E+F pattern of fibrosis, respectively. Thus, high levels of IFN‐γ have been associated with protection for individuals infected with schistosomiasis in endemic areas . Moreover, we identified significant correlations between IL‐2 and Th1 and Th2 cytokines in the groups with moderate fibrosis, suggesting a mixed response in patients with this degree of fibrosis.…”

“…This corroborates with Oliveira‐Prado et al . and Blum et al . who found high levels of IL‐4, IL‐6 and other Th1 cytokines.…”

Adults from Kisumu, Kenya have robust γδ T cell responses to Schistosoma mansoni, which are modulated by tuberculosis

“…In contrast, the proportion of individuals who respond to SWAP is consistent between groups of acute and chronically infected individuals [37]. In addition, PBMC from chronically infected individuals show higher cytokine production and phosphorylation of T cell signaling molecules following stimulation with SWAP than SEA [39,40]. It should be noted that while our results highlight a robust TH1 cytokine response to SWAP, previous studies in the region have found that PBMC and whole blood cultures stimulated with SWAP are capable of producing both TH1 and TH2 cytokines [41][42][43].…”