Human schistosomiasis mansoni: intensity of infection differentially affects the production of interleukin-10, interferon-γ and interleukin-13 by soluble egg antigen or adult worm antigen stimulated cultures

Abstract

The effect of the intensity of infection (eggs per gram faeces, epg) on the production of interferon-gamma (INF-gamma), interleukin (IL)-10 and IL-13 by peripheral blood mononuclear cells (PBMCs) from individuals living in a Schistosoma mansoni-endemic area was evaluated. In vitro stimulation of PBMCs with soluble egg antigen (SEA) resulted in significantly higher secretion levels of IFN-gamma in egg-negative individuals compared with those with an intensity of infection of more than 100 epg. In contrast, the egg-positive group produced significantly higher amounts of IL-10. Levels of IL-13 did not differ significantly between egg-positive and egg-negative groups. These findings suggest that IL-10 is an important cytokine in the control of the T helper cell (Th) type 1 responses during human S. mansoni infection, shifting the immune response from Th0 in egg-negative individuals from an endemic area to a Th2 polarization in chronic infected individuals.

Cytokine profile associated with chronic and acute human schistosomiasis mansoni

“…Our results showed low levels of IFN-γ production in infected patients with the IN clinical form of schistosomiasis (Zwingenberger et al 1991, Viana et al 1994, Silveira et al 2004. When compared to acute patients, we found higher IFN-γ levels detected in whole blood cultures stimulated with SEA or SWAP antigens from HS patients, which was also associated with degree II of hepatic fibrosis.…”

At Homeostasis Filarial Infections Have Expanded Adaptive T Regulatory but Not Classical Th2 Cells

“…Typically, however, at the time of patency (when egg laying occurs or microfilariae appear), type 1 responses are markedly downregulated, presumably allowing for expanded (or upregulated) type 2 responses (5–8). These data have found parallels in cross-sectional T cell analyses of patients with filarial or schistosome infection from acutely infected expatriates (9–12) as well as from chronically infected endemic populations (13–15). Techniques such as limiting dilution analysis (16) or ELISPOTS (17, 18) have demonstrated that there were lower frequencies of parasite-specific T cells capable of proliferating and producing IL-2 and IFN-γ in patients with patent lymphatic filariasis.…”

Hepatic stellate cells and parasite-induced liver fibrosis

“…In contrast, macrophages stimulated by Th2 cytokines, especially IL-13, become alternatively activated and produce arginase-1 (arg-1) and proline, higher levels of which are associated with larger granulomas and increased fibrosis [11]. Other factors associated with the development of fibrosis in schistosomiasis are repeated exposure [25] and intensity of infection [27]. In a study on human patients, an increase in egg deposition in chronically infected individuals was observed to shift the immune response from a Th0 to a Th2 response and this correlated with increased levels of IL-10 [27].…”

“…Other factors associated with the development of fibrosis in schistosomiasis are repeated exposure [25] and intensity of infection [27]. In a study on human patients, an increase in egg deposition in chronically infected individuals was observed to shift the immune response from a Th0 to a Th2 response and this correlated with increased levels of IL-10 [27]. Another study on S. mansoni- infected baboons demonstrated that repeated infection and treatment primed lymphocytes to produce increased levels of TGF-β and IL-4 which are known pro-fibrogenic cytokines [25].…”