The roles of supernatant of macrophage treated by excretory-secretory products from muscle larvae of Trichinella spiralis on the differentiation of C2C12 myoblasts

Authors: BAI, X - Chinese Center For Disease Control; WANG, XL - Jilin University; TANG, B - Chinese Center For Disease Control; BOIREAU, P - French Agency For Food, Environmental And Occupational Health & Safety (ANSES); Rosenthal, Benjamin; WU, XP - Chinese Center For Disease Control; LIU, MY - Jilin University; LIU, XL - Chinese Center For Disease Control

Submitted to: Veterinary Parasitology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/10/2016
Publication Date: 11/15/2016
Citation: Bai, X., Wang, X., Tang, B., Boireau, P., Rosenthal, B.M., Wu, X., Liu, M., Liu, X. 2016. The roles of supernatant of macrophage treated by excretory-secretory products from muscle larvae of Trichinella spiralis on the differentiation of C2C12 myoblasts. Veterinary Parasitology. 231: 83-91. doi: doi.org/10.1016/j.vetpar.2016.07.033.

Interpretive Summary: Consuming improperly cooked game confers risk for acquiring Trichinella parasites, the larvae of which induce host cells to tranform into "nurse cells." The process by which parasites induce such changes in mammalian cells is poorly understood; studying this process may yield insights into preventing or treating such infections, and may shed light on more general processes related to cell differentiation cancer, which these parasites have been shown can influence. Here, exposing cultured cells to products secreted by parasites activated several cellular processes and signaling pathways, providing greater clarity as to the mechanisms that induce the host cell to make a protective home for the parasite. In the future, the effectors responsible for these responses may be used to help prevent and/or treat these infections, and may even find application in regulating immune diseases and cancer.

Technical Abstract: The excretory-secretory products (ESPs) released by the muscle-larvae (ML) stage of Trichinella spiralis have been suggested to be involved in nurse cell formation. However, the molecular mechanisms by which ML-ESPs modulate nurse cell formation remain unclear. Macrophages exert either beneficial or deleterious effects on tissue repair, depending on their activation/polarization state. They are crucial for skeletal muscle repair, notably, via their actions on myogenic precursor cells. However, these interactions during T. spiralis infection have not been characterized. In the present study, the ability of conditioned medium (CM) from J774A.1 macrophages treated with ML-ESPs to influence the differentiation of murine myoblasts, and the mechanisms of this influence, were investigated in vitro. The results showed that the expression of Myogenic Regulatory Factors (MRFs) MyoD and myogenin, myosin heavy chain (MyHC), and the p21 cyclin-dependent kinase inhibitor were reduced in CM treated cells compared to their expression in the control group. These findings indicated that CM inhibited myoblast differentiation. Conversely, CM promoted myoblast proliferation and increased cyclin D1 levels. Taken together, results of our study suggested that CM can indirectly influence myoblast differentiation and proliferation, which provides a new method for the elucidation of the complex mechanisms involved in cell-parasite and cell–cell interactions during T. spiralis infection.