Macrophages activate fibroblasts to promote the collagen capsule formation during Trichinella spiralis infection

Trichinella spiralis (T. spiralis) can establish long-term infections within skeletal muscle cells, which are encapsulated by collagen capsule. Histological studies reveal that T. spiralis-infected muscle cells are surrounded by a significant number of inflammatory cells during the formation of collagen capsules. However, research has focused minimally on the role of inflammation in this process. In this study, mice were orally administered 300 muscle larvae per mouse and were euthanized weekly. The skeletal muscle was harvested. The quantity of macrophages, collagen deposition and the activated state of fibroblasts in the T. spiralis-infected muscle tissue were investigated using Masson’s trichrome staining, immunohistochemistry staining and western blot analysis. The macrophages were co-cultured with fibroblasts. Western blot analysis was conducted to confirm the type I collagen expression of fibroblasts. Then, the collagen deposition and activation status of fibroblasts were further confirmed through macrophage depletion in the infected muscle. The findings demonstrated that the expression levels of type I and IV collagen in the T. spiralis-infected muscle increased. Histological analyses showed a substantial presence of non-parenchymal cells embedded in areas of type I collagen deposition surrounding the infected muscle cells. These non-parenchymal cells included α-SMA⁺ myofibroblasts and CD206⁺macrophages. Type I collagen expression in fibroblasts increased when they were co-cultured with macrophages. Specific deletion of macrophages in the infected muscle resulted in reduced collagen deposition and a decreased number of α-SMA⁺myofibroblasts. These findings reveal that macrophages can regulate the activation of fibroblasts in the T. spiralis-infected muscle, leading to the production of type I collagen that constitutes the collagen capsule.