“…As schistosomiasis progresses, the majority of the infected individuals evolve to the asymptomatic (INT) form of the infection and modulate many of their specific immune responses [1,3]. In contrast, persons experiencing the acute phase or progressing to the severe chronic HS schistosomiasis, do not seem to develop the same modulatory mechanisms [26,27].…”
Section: Discussionmentioning
confidence: 99%
“…We believe that this mechanism could operate to decrease the cellular reactivity in different compartments of the immune system modulating the granuloma formation. Although the immune response at different compartments might be potentially distinct, it has been demonstrated that the modulation of the anti-SEA response, which is observed at the PBMC level [1,3], is also observed at the granuloma level [41]. In addition, studies using the experimental mouse model [42] have shown a role for IL-10 in diminishing the granuloma formation, and consequently the pathology in mice infected with S. mansoni.…”
Section: Discussionmentioning
confidence: 99%
“…On the other hand, PBMC responses from severe or hospitalized HS patients are significantly lower. In contrast, the responses to soluble adult worm antigens (SWAP) are not distinguishable between INT or HS groups of patients [3,4].…”
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.
“…As schistosomiasis progresses, the majority of the infected individuals evolve to the asymptomatic (INT) form of the infection and modulate many of their specific immune responses [1,3]. In contrast, persons experiencing the acute phase or progressing to the severe chronic HS schistosomiasis, do not seem to develop the same modulatory mechanisms [26,27].…”
Section: Discussionmentioning
confidence: 99%
“…We believe that this mechanism could operate to decrease the cellular reactivity in different compartments of the immune system modulating the granuloma formation. Although the immune response at different compartments might be potentially distinct, it has been demonstrated that the modulation of the anti-SEA response, which is observed at the PBMC level [1,3], is also observed at the granuloma level [41]. In addition, studies using the experimental mouse model [42] have shown a role for IL-10 in diminishing the granuloma formation, and consequently the pathology in mice infected with S. mansoni.…”
Section: Discussionmentioning
confidence: 99%
“…On the other hand, PBMC responses from severe or hospitalized HS patients are significantly lower. In contrast, the responses to soluble adult worm antigens (SWAP) are not distinguishable between INT or HS groups of patients [3,4].…”
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.
“…However, during chronic infection, inflammatory cytokine responses to Schistosoma soluble egg antigens (SEAs) are much reduced (202), while Th2 cytokines (including IL-10) are upregulated (39,63), and only a small proportion of patients progress to severe hepatosplenic disease. Both acute schistosomiasis patients and severe pathology cases mount much stronger T cell proliferative responses to SEA than low-pathology but chronically infected individuals (98); the low-pathology group, however, has higher frequencies of CD4 ϩ CD25 high Tregs (282). The production of Th2 cytokines (especially IL-13), although required for resistance, can also have detrimental effects, as they are important for the generation of fibrosis and pathology in the liver and spleen during chronic schistosomiasis (62,64).…”
Section: Immune Regulation and Spectrum Of Diseasementioning
SUMMARY
Helminth parasites infect almost one-third of the world's population, primarily in tropical regions. However, regions where helminth parasites are endemic record much lower prevalences of allergies and autoimmune diseases, suggesting that parasites may protect against immunopathological syndromes. Most helminth diseases are spectral in nature, with a large proportion of relatively asymptomatic cases and a subset of patients who develop severe pathologies. The maintenance of the asymptomatic state is now recognized as reflecting an immunoregulatory environment, which may be promoted by parasites, and involves multiple levels of host regulatory cells and cytokines; a breakdown of this regulation is observed in pathological disease. Currently, there is much interest in whether helminth-associated immune regulation may ameliorate allergy and autoimmunity, with investigations in both laboratory models and human trials. Understanding and exploiting the interactions between these parasites and the host regulatory network are therefore likely to highlight new strategies to control both infectious and immunological diseases.
“…This decrease has been suggested to be due to the regulation of the immune response to the parasite eggs trapped in the tissues. Analysis of the cellular immune response of individuals with the severe form of the disease (hepatosplenic schistosomiasis) has demonstrated that those with the compensated form have an increased response to SEA while patients with the decompensated form show a significant decrease in the response to both SEA and SWAP, thus being considered non-responders (3,4).…”
The role of different cytokines in the peripheral blood mononuclear cell (PBMC) proliferative response and in in vitro granuloma formation was evaluated in a cross-sectional study with patients with the different clinical forms and phases of Schistosoma mansoni infection, as well as a group of individuals naturally resistant to infection named normal endemic (NE). The blockage of IL-4 and IL-5 using anti-IL-4 and anti-IL-5 antibodies significantly reduced the PBMC proliferative response to soluble egg (SEA) and adult worm (SWAP) antigens in acute (ACT), chronic intestinal (INT) and hepatosplenic (HS) patients. Similar results were obtained in the in vitro granuloma formation. Blockage of IL-10 had no significant effect on either assay using PBMC from ACT or HS. In contrast, the addition of anti-IL-10 antibodies to PBMC cultures from INT patients significantly increased the proliferative response to SEA and SWAP as well as the in vitro granuloma formation. Interestingly, association of anti-IL-4 and anti-IL-10 antibodies did not increase the PBMC proliferative response of these patients, suggesting that IL-10 may act by modulating IL-4 and IL-5 secretion. Addition of recombinant IL-10 decreased the proliferative response to undetectable levels when PBMC from patients with the different clinical forms were used. Analysis of IFN-γ in the supernatants showed that PBMC from INT patients secreted low levels of IFN-γ upon antigenic stimulation. In contrast, PBMC from NE secreted high levels of IFN-γ. These data suggest that IL-10 is an important cytokine in regulating the immune response and possibly controlling morbidity in human schistosomiasis mansoni, and that the production of IFN-γ may be associated with resistance to infection.
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