Trichinella spiralis is recognized for its ability to regulate host immune responses via excretory/secretory (ES) products.
Serine protease inhibitors (
serpins) play an important role in ES product-mediated immunoregulatory effects during T. spiralis
infection. In this study, the immunoregulatory properties of a
serpin derived from T. spiralis (Ts-
serpin) were explored in BALB/c mice. The results showed that naturally occurring Ts-
serpin was detected in the stichosomes of muscle larvae and adult worms. Moreover, enhancing (by injection of a soluble-expressed recombinant Ts-
serpin [rTs-
serpin]) or blocking (by passive immunization with anti-rTs-
serpin serum) the effects of Ts-
serpin changed the levels of
cytokines related to
inflammation induced by T. spiralis
infection in the serum, mesenteric lymph nodes, and peritoneal cavity, which then led to a change in the adult worm burden in early T. spiralis
infection. Moreover, the phenotypic changes in peritoneal macrophages were found to be related to Ts-
serpin-mediated immunoregulation. Furthermore, a STAT6 activation mechanism independent of IL-4Rα has been found to regulate
protein-mediated alternative activation of bone marrow-derived macrophages and mimic the immunoregulatory role of Ts-
serpin in T. spiralis
infection. Finally, the anti-inflammatory properties of rTs-
serpin and bone marrow-derived macrophage alternative activation by rTs-
serpin were demonstrated using a trinitrobenzene
sulfonic acid-induced
inflammatory bowel disease model. In summary, a
protein-triggered anti-inflammatory mechanism was found to favor the survival of T. spiralis in the early stage of
infection and help to elucidate the immunoregulatory effects of T. spiralis on the host immune response.