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Trichinella spiralis is an important foodborne parasitic nematode distributed worldwide that infects humans and animals. Glutaminase (GLS) is an important gene in the glutamine-dependent acid resistance (AR) system; however, its role in T. spiralis muscle larvae (ML) remains unclear. The present study aimed to characterize T. spiralis GLS (TsGLS) and assess its function in T. spiralis ML AR both in vitro and in vivo using RNA interference. The results indicated that native TsGLS (72 kDa) was recognized by anti-rTsGLS serum at the muscle larvae stage; moreover, an immunofluorescence assay confirmed that TsGLS was located in the epidermis of ML. After silencing the TsGLS gene, the relative expression of TsGLS mRNA and the survival rate of T. spiralis ML were reduced by 60.11% and 16.55%, respectively, compared to those in the PBS and control groups. In vivo AR assays revealed that the worm numbers at 7 and 35 days post-infection (dpi) decreased by 61.64% and 66.71%, respectively, compared to those in the PBS group. The relative expression of TsGLS mRNA in F1 generation T. spiralis ML was reduced by 42.52%, compared to that in the PBS group. To the best of our knowledge, this is the first study to report the presence of the glutamine-dependent AR system in T. spiralis. Our results indicate that TsGLS plays a crucial role in the T. spiralis AR system; thus, it could be used as a potential candidate target molecule for producing vaccines against T. spiralis infection.

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Antibodies targeting IL-23 or IL-17 are highly effective in the treatment of psoriasis and psoriatic arthritis, validating the RORγt /Th17 pathway in human disease. VTP-43742 is a potent, selective and orally active inhibitor of RORgt that is being pursued as a treatment of autoimmune disorders. Herein, we present data showing the effects of VTP-43742 in two separate mouse studies using the MOG35-55/CFA immunized EAE model. In a subchronic study, prophylactic dosing of VTP-43742 for 11 days gave a dose-dependent suppression of both CD4+IL-17+IFNγ- and CD4+IL-17+IFNγ+ T cells in spleen and in draining lymph nodes. Splenocytes from these mice restimulated in vitro with the MOG35-55 peptide showed specific suppression of Th17 derived cytokines. In a chronic disease study, the maximal pharmacological effect of VTP-43742 was compared to maximal IL-17 blockade by mouse monoclonal antibody MM17F3 (eBioscience) in a prophylactic setting. High dose VTP-43742 completely suppressed the EAE clinical score, significantly beyond the reduction seen with MM17F3 (p<0.001). Analysis of spinal cord RNA showed significant suppression of Th17-associated markers by VTP-43742 with no significant reduction by MM17F3. Additionally, spinal cord histology showed qualitatively greater suppression of demyelination and inflammatory cell infiltration with VTP-43742 treatment versus MM17F3, suggesting that RORγt blockade may provide treatment benefit beyond anti-IL-17 targeted strategies in autoimmunity.