Does helminth activation of Toll-Like Receptors modulate immune response in Multiple Sclerosis patients?
Multiple sclerosis (MS) is an inflammatory autoimmune demyelinating disease affecting the Central Nervous System, in which Th1 and Th17 cells appear to recognize and react against certain myelin sheath components.Epidemiological evidence has accumulated indicating steady increase in autoimmune disea...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2012-08-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fcimb.2012.00112/full |
| _version_ | 1818504459517427712 |
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| author | Jorge eCorreale Mauricio Franco Farez |
| author_facet | Jorge eCorreale Mauricio Franco Farez |
| author_sort | Jorge eCorreale |
| collection | DOAJ |
| description | Multiple sclerosis (MS) is an inflammatory autoimmune demyelinating disease affecting the Central Nervous System, in which Th1 and Th17 cells appear to recognize and react against certain myelin sheath components.Epidemiological evidence has accumulated indicating steady increase in autoimmune disease incidence in developed countries. Reduced infectious disease prevalence in particular has been proposed as the cause. In agreement with this hypothesis, we recently demonstrated significantly better clinical and radiological outcome in helminth-infected MS patients, compared to uninfected ones. Parasite-driven protection was associated with regulatory T cell induction and anti-inflammatory cytokine secretion, including increased TGF-β and IL-10 levels. Interestingly, surface expression of TLR2, on both B cells and dendritic cells (DC) was significantly higher in infected MS patients. Moreover, stimulation of myelin-specific T cell lines with a TLR2 agonist induced inhibition of T cell proliferation, suppression of IFN-γ, IL-12 and IL-17 secretion, as well as increase in IL-10 production, suggesting the functional responses observed correlate with TLR2 expression patterns. Furthermore, parasite antigens were able to induce TLR2 expression on both B cells and DCs. All functional effects mediated by TLR2 were abrogated when MyD88 gene expression was silenced; indicating helminth–mediated signaling induced changes in cytokine secretion in a MyD88-dependent manner.In addition, helminth antigens significantly enhanced co-stimulatory molecule expression, effects not mediated by MyD88. Parasite antigens acting on MyD88 induced significant ERK kinase phosphorylation in DC. Addition of the ERK inhibitor U0126 was associated with dose-dependent IL-10 inhibition and reciprocal enhancement in IL-12, both correlating with ERK inhibition. Finally, cytokine effects and changes observed in co-stimulatory DC molecules after helminth antigen exposure were lost when TLR2 was sile |
| first_indexed | 2024-12-10T21:37:23Z |
| format | Article |
| id | doaj.art-e5bf504f781541ddb40355f531988339 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-10T21:37:23Z |
| publishDate | 2012-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-e5bf504f781541ddb40355f5319883392022-12-22T01:32:37ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882012-08-01210.3389/fcimb.2012.0011232236Does helminth activation of Toll-Like Receptors modulate immune response in Multiple Sclerosis patients?Jorge eCorreale0Mauricio Franco Farez1Raúl Carrea Institute for Neurological Research, FLENIRaúl Carrea Institute for Neurological Research, FLENIMultiple sclerosis (MS) is an inflammatory autoimmune demyelinating disease affecting the Central Nervous System, in which Th1 and Th17 cells appear to recognize and react against certain myelin sheath components.Epidemiological evidence has accumulated indicating steady increase in autoimmune disease incidence in developed countries. Reduced infectious disease prevalence in particular has been proposed as the cause. In agreement with this hypothesis, we recently demonstrated significantly better clinical and radiological outcome in helminth-infected MS patients, compared to uninfected ones. Parasite-driven protection was associated with regulatory T cell induction and anti-inflammatory cytokine secretion, including increased TGF-β and IL-10 levels. Interestingly, surface expression of TLR2, on both B cells and dendritic cells (DC) was significantly higher in infected MS patients. Moreover, stimulation of myelin-specific T cell lines with a TLR2 agonist induced inhibition of T cell proliferation, suppression of IFN-γ, IL-12 and IL-17 secretion, as well as increase in IL-10 production, suggesting the functional responses observed correlate with TLR2 expression patterns. Furthermore, parasite antigens were able to induce TLR2 expression on both B cells and DCs. All functional effects mediated by TLR2 were abrogated when MyD88 gene expression was silenced; indicating helminth–mediated signaling induced changes in cytokine secretion in a MyD88-dependent manner.In addition, helminth antigens significantly enhanced co-stimulatory molecule expression, effects not mediated by MyD88. Parasite antigens acting on MyD88 induced significant ERK kinase phosphorylation in DC. Addition of the ERK inhibitor U0126 was associated with dose-dependent IL-10 inhibition and reciprocal enhancement in IL-12, both correlating with ERK inhibition. Finally, cytokine effects and changes observed in co-stimulatory DC molecules after helminth antigen exposure were lost when TLR2 was silehttp://journal.frontiersin.org/Journal/10.3389/fcimb.2012.00112/fullCytokinesHelminthsMultiple SclerosisParasitesToll-Like ReceptorsMyD88 |
| spellingShingle | Jorge eCorreale Mauricio Franco Farez Does helminth activation of Toll-Like Receptors modulate immune response in Multiple Sclerosis patients? Frontiers in Cellular and Infection Microbiology Cytokines Helminths Multiple Sclerosis Parasites Toll-Like Receptors MyD88 |
| title | Does helminth activation of Toll-Like Receptors modulate immune response in Multiple Sclerosis patients? |
| title_full | Does helminth activation of Toll-Like Receptors modulate immune response in Multiple Sclerosis patients? |
| title_fullStr | Does helminth activation of Toll-Like Receptors modulate immune response in Multiple Sclerosis patients? |
| title_full_unstemmed | Does helminth activation of Toll-Like Receptors modulate immune response in Multiple Sclerosis patients? |
| title_short | Does helminth activation of Toll-Like Receptors modulate immune response in Multiple Sclerosis patients? |
| title_sort | does helminth activation of toll like receptors modulate immune response in multiple sclerosis patients |
| topic | Cytokines Helminths Multiple Sclerosis Parasites Toll-Like Receptors MyD88 |
| url | http://journal.frontiersin.org/Journal/10.3389/fcimb.2012.00112/full |
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