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.
Highlights
Neurocysticercosis (NCC) is the most severe form of the diseases caused by Taenia solium, and remains to be the major cause of epileptic seizures in developing countries such as Mexico
Macrophages exposed to solium GST fraction (SGSTF) express M1 activation markers
In order to determine whether SGSTF may directly activate peritoneal macrophages, we exposed them to SGSTF for 24 h and compared the expression of several markers to those obtained from the non-stimulated control (c), M(LPS), and M(Tc-8w) macrophages
Summary
Neurocysticercosis (NCC) is the most severe form of the diseases caused by Taenia solium, and remains to be the major cause of epileptic seizures in developing countries such as Mexico. The macrophages exhibit an alternatively activated phenotype with the ability to block lymphocyte proliferative response and express high levels of chitinase-like 3 (Chil3) type 1 (Ym1) and arginase 1 (Arg1), likewise programmed c 2019 The Author(s).
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