Cytokine Regulation of Human Immune Response to Schistosoma mansoni: Analysis of the Role of IL‐4, IL‐5 and IL‐10 on Peripheral Blood Mononuclear Cell Responses

Abstract

The role of cytokines on the in vitro proliferative response of peripheral blood mononuclear cells (PBMC) from Schistosoma mansoni infected patients to soluble egg (SEA) and adult worm antigens (SWAP) were evaluated. The results obtained demonstrated that the proliferative response of PBMC from chronic intestinal (INT) patients to SEA and SWAP is increased by the blockage of IL-10 with specific monoclonal antibodies (MAb). The effects of these antibodies were readily reversed by the addition of recombinant IL-10. In contrast, no effect was observed on the PBMC response of acute and hepatosplenic patients (HS) in the presence of anti-IL-10. Anti-IL-4 antibodies decreased the PBMC response of the intestinal (INT) and HS individuals to SEA and SWAP, and the PBMC response of acute patients to SEA but not to SWAP. Addition of anti-IL-5 MAb did not decrease the PBMC response of acute patients to SEA or SWAP. These results suggested that IL-10 has an important role in the modulation of the immune response in chronic asymptomatic patients and that this cytokine may be an important factor in controlling morbidity.

Enhanced Egg-Induced Immunopathology Correlates With High IFN-γ in Murine Schistosomiasis: Identification of Two Epistatic Genetic Intervals

“…Schistosome Ag-reactive T cell clones, derived from individuals homozygous for the allele that determines susceptibility, tended to be of the Th0/Th1 type, whereas those derived from individuals homozygous for the resistance allele, tended to be of the Th0/Th2 type (19). This observation is in agreement with field reports suggesting that the more severe clinical presentations of human schistosomiasis, including the acute form of schistosomiasis, tend to correlate with a cytokine balance tilted in the Th1 direction (51)(52)(53)(54)(55)(56).…”

Cellular and Humoral Immune Responses and Protection against Schistosomes Induced by a Radiation-Attenuated Vaccine in Chimpanzees

“…It needs to be emphasized that this down-modulation of immune responses occurred in vaccinated chimpanzees before oviposition. Nevertheless, in humans with intestinal schistosomiasis, IL-10 is secreted by PBMC, particularly in response to egg antigens (5,37,67), which were also the most efficient inducers in our own study. A major task is to identify the crossreactive components responsible for driving IL-10 production, with glycan epitopes being likely candidates (62).…”

“…Only after oviposition was there a marked elevation in cellular reactivity, which signaled the start of the acute stage, with the simultaneous secretion of IFN-␥ and IL-5 by PBMC; the egg antigen-driven type 2 response quickly came to dominate. There are parallels here with human schistosomiasis, in which PBMC sampled from patients at the acute stage of the disease show strong proliferative responses and IFN-␥ secretion (37,41). In contrast, PBMC from patients with chronic intestinal schistosomiasis secrete hardly any IFN-␥ (63) but secrete significant amounts of IL-5 (5, 39).…”

Schistosoma mansoni infection modulates the immune response against allergic and auto-immune diseases

“…mansoni infection in mice models lead to an initial Th1 response with production of interferon-γ (IFN-γ), that is followed by a Th2 response induced by the parasite eggs' antigens, that stimulates IL-10 production . In humans the immune response in the acute phase is also associated with Th1 response with increased production of tumor necrosis factor (TNF-α) and IFN-γ (de Jesus et al 2002), while in the chronic phase the immune response is the Th2 type, with elevated levels of IL-4, IL-5, and IL-10 and decreased levels of IFN-γ (Araujo et al 1994, Malaquias et al 1997, Joseph et al 2004). …”