Taenia solium glutathione transferase fraction activates macrophages and favors the development of Th1-type response

Abstract

Glutathione (GSH) transferase (GST) is an essential enzyme in cestodes for the detoxification of xenobiotics. In Taenia solium, two GSTs (Ts25GST and Ts26GST kDa) were isolated as a fraction (SGSTF) by GSH-Sepharose-4B. Both are located on the tegument. Immunization assays with SGSTF reduced up to 90% of the parasitic load in a murine model of cysticercosis. It prompted us to investigate how SGSTF induces this protective immune response. To test it, we exposed peritoneal macrophages to SGSTF for 24 h; such exposure favored the production of IL-12, TNF, and IL-10 as well as the expression of nitric oxide synthase 2 inducible (Nos2) and CD86, but did not induce the expression of chitinase-like 3 (Chil3). Confocal microscopy showed that the macrophages internalize the SGSTF which co-localized after 1 h with MHC-II in their plasma membranes. Macrophages exposed to SGSTF and co-cultured with anti-CD3 pre-activated T CD4+ cells, enhanced the proliferation of CD4+ cells, induced high interferon-γ (IFN-γ) secretion, and elevated the expression of CD25 and CD69, molecules associated with cell activation. Similar assay using T CD4+ cells from DO11.10 mice and ovalbumin (OVA) peptide+SGSTF as stimuli, showed enhanced cell proliferation and OVA-specific IFN-γ secretion. These data are in-line with those indicating that the P1, P5, and P6 peptides of Schistosoma japonicum 28GST highly promote T-cell proliferation and Th1 response in vitro. We found that such peptides are also present on Ts25GST and Ts26GST. It suggests that SGSTF activates peritoneal macrophages to a classically activated-like phenotype, and that these macrophages induce the differentiation of T CD4+ cells toward a Th1-type response.

Taenia soliumandTaenia crassiceps: miRNomes of the larvae and effects of miR-10-5p and let-7-5p on murine peritoneal macrophages

“…Naive murine macrophages were isolated from the peritoneum by aspiration with RPMI and 2 × 10 6 cells/ml were seeded on sterilized coverslips coated with poly- d -lysine (Neuvitro, Vancouver, WA, U.S.A.) in a culture plate, as previously described [28]. Cultures were incubated in RPMI-1640 with 10% FBS, 100 U/ml penicillin, and 100 μg streptomycin in an atmosphere of 5% CO 2 at 37°C for 15, 30, or 60 min in the absence or presence of synthetic miR-10-5p or let-7-5p (100 ng/ml) coupled to Cyanine 5 (Cy5) (Sigma, St Louis, MO, U.S.A.).…”

Molecular characterization and tissue localization of glutathione S-transferase from adult Ancylostoma ceylanicum

“…Recombinant Ac -GST was highly immunogenic in vaccinated animals and induced not only Th2-associated antibody (IgG1) and cytokine (IL-4) responses but also a strong Th1-like response (Zhan et al ., 2005). In addition, the GSH transferase fraction from Taenia solium activated macrophages and induced the differentiation of CD4 + T cells toward a Th1-type response (Vega-Angeles et al ., 2019). Free haem is the end product of haemoglobin digestion in the blood-feeding parasites, which produce oxygen free radicals potentially toxic to the parasite (Klonis et al ., 2011).…”

Development of New Drugs to TreatTaenia soliumCysticercosis: Targeting 26 kDa Glutathione Transferase

“…parasite cGSTs [20]. Ts26GST has ligandin activity and is internalized by macrophages, suggesting an important role in transport and the parasite-host relationship [72,73].…”