Importance of TLR2 in the direct response of T lymphocytes to Schistosoma mansoni antigens

Abstract

The immunomodulatory effect of Schistosoma mansoni antigens has often been attributed to interaction with PRR expressed on APC. Our previous work has shown that S. mansonisoluble egg antigen (SEA) can induce, together with a Th2 response, TGF-b-dependent Foxp3 expression in naïve CD4 1 T cells from NOD mice. We found that SEA can directly upregulate the expression of surface-bound TGF-b in purified CD4 1 T cells in the absence of accessory cell interactions. In this study, we show that the C-type lectin receptors DEC-205 and galectin-3 were involved in the direct interaction between S. mansoni antigens and CD4 1 T cells. SEA was able to enhance CD4 1 T-cell secretion of bioactive TGF-b in response to TLR2 ligand stimulation, in the absence of APC. We also show that TLR2 expressed on CD4 1 T cells was important for the Foxp3 expression induced by SEA.

Effects of soluble extracts from Leishmania infantum promastigotes, Toxoplasma gondii tachyzoites on TGF-β mediated pathways in activated CD4+ T lymphocytes

“…Schistosoma mansoni soluble egg antigen (SEA) directly act on CD4 þ T cells via TLR2 to induce the secretion of bioactive TGF-b [40]. P. falciparum extracts activate TGF-b receptor activation through membrane bound TGFb molecules and TGF-b dependent signals positively regulate TGF-b expression [41].…”

The S. mansoni glycoprotein ω‐1 induces Foxp3 expression in NOD mouse CD4+ T cells

“…Specific molecules including integrins and proteolytic enzymes provide various mechanisms to regulate TGF-b activation [21]. We have previously used LAP as an indicator of TGF-b on the cell surface of CD4 1 T cells [16,17]. x-1 enhances TGF-b secretion and RA converting enzyme expression in LPS-stimulated DCs…”

OdDHL Inhibits T Cell Subset Differentiation and Delays Diabetes Onset in NOD Mice

“…This mode of action in diabetes prevention is similar to that found with helminth modulation of autoimmune disease, where effects are seen only at early time points. However, in the case of helminth infection, there is additional evidence of induction of Treg and invariant NK T (iNKT) cells to maintain an inhibition of diabetes prevention (5,15). It should also be noted that OdDHL does not mediate the profound diabetes prevention observed with helminth-derived products, which would be consistent with a lack of induction of robust immunoregulatory circuits by OdDHL.…”

“…Studies using animal models have demonstrated protection against autoimmune encephalomyelitis (EAE) and type 1 diabetes following some bacterial, viral, or helminth infections (3,6,7,14,25,27,30). It has also been demonstrated that a live infection may not be necessary for protection against type 1 diabetes, and parasite-derived products such as the soluble egg antigen (SEA) and soluble worm antigen (SWA) fractions of Schistosoma mansoni (5,29) as well as some bacterial components (1,17) can also be effective.…”

“…Alongside a change in T helper cell bias, more recent studies with SEA have shown that this helminth extract, through its action on dendritic cells (DCs), is able to induce Foxp3 expression in naïve NOD T cells (28). As regulatory T (Treg) cells have been implicated in the protection against type 1 diabetes in NOD mice (4), this provides an additional mechanism by which infections can inhibit diabetes onset in NOD mice (5,16,18).…”