The Anti-Inflammatory Immune Response in Early Intestinal Infection Depends on Serine Protease Inhibitor-Mediated Alternative Activation of Macrophages.

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 infection. In this study, the immunoregulatory properties of a serpin derived from (-serpin) were explored in BALB/c mice. The results showed that naturally occurring -serpin was detected in the stichosomes of muscle larvae and adult worms. Moreover, enhancing (by injection of a soluble-expressed recombinant -serpin [r-serpin]) or blocking (by passive immunization with anti-r-serpin serum) the effects of -serpin changed the levels of cytokines related to inflammation induced by infection in the serum, mesenteric lymph nodes, and peritoneal cavity, which then led to a change in the adult worm burden in early infection. Moreover, the phenotypic changes in peritoneal macrophages were found to be related to -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 -serpin in infection. Finally, the anti-inflammatory properties of r-serpin and bone marrow-derived macrophage alternative activation by r-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 in the early stage of infection and help to elucidate the immunoregulatory effects of on the host immune response.