Inhibition of mammalian muscle differentiation by excretory secretory products of muscle larvae of Trichinella spiralis in vitro

Abstract

The excretory-secretory products (ESP) released by muscle stage of Trichinella spiralis have been suggested to be involved in nurse cell formation. However, the molecular mechanisms by which ESP modulate nurse cell formation remain unclear. In the present study, the ability of ESP of muscle larvae of T. spiralis (ML-ESP) to influence the proliferation and differentiation of murine myoblasts and the mechanisms were evaluated in vitro using C2C12 myoblast cell line, which were incubated for various times under grow or differentiation culture medium containing various concentrations of ML-ESP. The results indicated that ML-ESP promoted myoblast proliferation in a dose-dependent manner and increased the expression of the cell-cycle regulator cyclin D1 as well as that of proliferating cell nuclear antigen (PCNA). Conversely, ML-ESP inhibited the differentiation of these cells, which was evidenced by a reduction in the levels of MHC and MRFs expression (MyoD and myogenin) as well as that of p21. In addition, ML-ESP also inhibited the phosphorylation of p38 MAPK in differentiating C2C12 myoblast. Taken together, these results imply that certain critical mediators contained in ML-ESP inhibit myogenesis through enhancing skeletal myoblasts proliferation and down-regulating the expression of MRFs as well as involving p38 MAPK signalling pathway, which provides insight into the mechanisms utilised by T. spiralis to interfere normal wound repair in infected muscle cells and affect nurse cell formation.

Genome analysis of Excretory/Secretory proteins in Taenia solium reveals their Abundance of Antigenic Regions (AAR)

“…Tapeworms (Platyhelminthes, Cestoda) secrete several ES molecules to regulate the host immune system for parasite survival 13 14 15 16 17 18 19 . ES proteins involved in the uptake and sequestration of host hydrophobic molecules 20 and mediating the host immune response to parasite infection 21 have been experimentally characterized in different life cycle stages of T. solium 22 .…”

Partially Protective Immunity Induced by a 20 kDa Protein Secreted by Trichinella spiralis Stichocytes

“…The ES antigens of T . spiralis are directly exposed to the host's immune system and are the main antigens that induce the immune responses in the host [ 42 ]. It has been reported that the ES products of T .…”

Secretory Products ofTrichinella spiralisMuscle Larvae and Immunomodulation: Implication for Autoimmune Diseases, Allergies, and Malignancies

“…ES L1 originate from stichocyte granules in the stichosome, secretory organelle of the T. spiralis ML [14]. These products participate in the interaction with various host cells such as enterocytes, muscle cells, and immune cells, thus achieving their role in parasitism and immune response induction and modulation [10, 15]. Through ES L1 the parasite creates an environment suitable for its own survival, by either modulation of host immune response or influencing host cell gene expression.…”

“…Although it has been assumed that T. spiralis ES L1 actively participate in nurse cell formation, the real evidence emerged from in vitro studies using C2C12 myoblast cell line, incubated with these products. It was shown that ES L1 promote myoblasts proliferation and at the same time inhibited their differentiation [15]. However, little is known about molecular mechanisms underlying dedifferentiation of the damaged muscle cells and misdifferentiation of the satellite cells after larvae invasion.…”