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From: Kofi on 6 Jun 2010 00:05
When sympathetic nerves are damaged in the first place as is the case in
chronic colitis and arthritis, this may compromise the TLR2 signaling
necessary for helminths to induce tolerance to self and innocuous
allergens/antigens like molds and wheat.
Eur J Immunol. 2009 Nov;39(11):3052-65
CD4+CD25+ Treg induction by an HSP60-derived peptide SJMHE1 from
Schistosoma japonicum is TLR2 dependent.
Wang X, Zhou S, Chi Y, Wen X, Hoellwarth J, He L, Liu F, Wu C, Dhesi S,
Zhao J, Hu W, Su C.
Department of Pathogen Biology & Immunology, Department of Pharmacology,
Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University,
Nanjing, Jiangsu, PR China.
Chronic schistosome infection results in the suppression of host immune
responses, allowing long-term schistosome survival and restricting
pathology. Current theories suggest that Treg play an important role in
this regulation. However, the mechanism of Treg induction during
schistosome infection is still unknown. The aim of this study was to
determine the mechanism behind the induction of CD4(+)CD25(+) T cells by
Schistosoma japonicum HSP60 (SjHSP60)-derived peptide SJMHE1 as well as
to elucidate the cellular and molecular basis for the induction of
CD4(+)CD25(+) T cells during S. japonicum infection. Mice immunized with
SJMHE1 or spleen and LN cells from naive mice pretreated with SJMHE1 in
vitro all displayed an increase in CD4(+)CD25(+) T-cell populations.
Release of IL-10 and TGF-beta by SJMHE1 stimulation may contribute to
suppression. Adoptively transferred SJMHE1-induced CD4(+)CD25(+) T cells
inhibited delayed-type hypersensitivity in BALB/c mice. Additionally,
SJMHE1-treated APC were tolerogenic and induced CD4(+) cells to
differentiate into suppressive CD4(+)CD25(+) Treg. Furthermore, our data
support a role for TLR2 in SJMHE1-mediated CD4(+)CD25(+) Treg induction.
These findings provide the basis for a more complete understanding of
the S. japonicum-host interactions that contribute to host homeostatic
mechanisms, preventing an excessive immune response.
* Research Support, Non-U.S. Gov't
J Immunol. 2009 Nov 1;183(9):5999-6012. Epub 2009 Oct 7.
Helminth antigens modulate immune responses in cells from multiple
sclerosis patients through TLR2-dependent mechanisms.
Correale J, Farez M.
Dr. Raul Carrea Institute for Neurological Research, Foundation for the
Fight against Childhood Neurological Diseases (FLENI), Department of
Neurology, Buenos Aires, Argentina.
To better understand the link between parasite infections and the course
of multiple sclerosis (MS), we studied the role of TLRs in helminth
product recognition by dendritic cells (DCs) and B cells. Baseline
expression of TLR2 was significantly higher in infected-MS patients
compared with uninfected MS subjects or healthy controls. Moreover,
cells exposed to TLR2 agonists or to soluble egg Ag (SEA) from
Schistosoma mansoni resulted in significant TLR2 up-regulation. SEA
suppressed the LPS-induced DCs production of IL-1beta, IL-6, IL-12, and
TNF-alpha and enhanced TGF-beta as well as IL-10 production. Similarly,
after exposure to SEA, anti-CD40-activated B cells increased IL-10
production. Both processes were MyD88 dependent. In addition, SEA
down-regulated the expression of LPS-induced costimulatory molecules on
DCs in a MyD88-independent manner. DCs stimulation by SEA and TLR2
agonists induced increasing phosphorylation of the MAPK ERK1/2. Neither
stimulus showed an effect on p38 and JNK1/2 phosphorylation, however.
Addition of the ERK1/2 inhibitor U0126 was associated with
dose-dependent inhibition of IL-10 and reciprocal enhancement of IL-12.
Finally, cytokine effects and changes observed in DCs costimulatory
molecule expression after SEA exposure were lost when TLR2 expression
was silenced. Overall, these findings indicate that helminth molecules
exert potent regulatory effects on both DCs and B cells through TLR2
regulation conducted via different signaling pathways. This knowledge
could prove critical in developing novel therapeutic approaches for the
treatment of autoimmune diseases such as MS.
* Research Support, Non-U.S. Gov't