GMI, an Immunomodulatory Peptide from Ganoderma microsporum, Restrains Periprosthetic Joint Infections via Modulating the Functions of Myeloid-Derived Suppressor Cells and Effector T Cells

Abstract

Periprosthetic joint infections (PJIs) caused by Staphylococcus aureus infection are difficult to treat due to antibiotic resistance. It is known that the biofilms from methicillin-resistant S. aureus (MRSA) promote expansion of myeloid-derived suppressor cells (MDSCs) to suppress T-cell proliferation and benefit bacterial infections. This study finds that GMI, a fungal immunomodulatory peptide isolated from Ganoderma microsporum, suppresses MDSC expansion to promote the proliferation of cytotoxic T cells. The enhancement is likely attributed to increased expression of IL-6 and TNF-α and reduction in ROS expression. Similar beneficial effects of GMI on the suppression of MDSC expansion and IL-6 expression are also observed in the whole blood and reduces the accumulation of MDSCs in the infected bone region in a mouse PJI infection model. This study shows that GMI is potentially useful for treating S. aureus-induced PJIs.

Ganoderma microsporum immunomodulatory protein acts as a multifunctional broad-spectrum antiviral against SARS-CoV-2 by interfering virus binding to the host cells and spike-mediated cell fusion

“…The relationship between GMI and human body immunity is also noteworthy as it has been mentioned in various articles. GMI could restrict MDSC expansion to induce the proliferation of cytotoxic T cells [64] . In addition, GMI has been shown to have similar protein sequence and structure in comparison with Lingzhi 8 (LZ8) from Ganoderma microsporum.…”

Safety assessment of the fungal immunomodulatory protein from Ganoderma microsporum (GMI) derived from engineered Pichia pastoris: Genetic toxicology, a 13-week oral gavage toxicity study, and an embryo-fetal developmental toxicity study in Sprague-Dawley rats

“…A 2.0 Å structure of GMI was solved and GMI showed a dimer:dimer quaternary structure with non-covalent interactions through the N-terminal helices (PDB ID 3KCW, [16] ). Furthermore, GMI with the same quality were evaluated in the platform for the anti-tumor activity and immunomodulation under immune disorder/disease model, and GMI showed a variety of bioactivities in the application for oncology [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [44] , [43] , immuno-oncology [53] , [54] , [55] , [56] , [57] , and immunology [59] , [60] , [62] , [63] , [64] , [61] , [58] , [65] . Although these promising findings are attractive for the further clinical application, the quality and the safety are always the major concerns.…”

A Review of Chemical Composition and Bioactivity Studies of the Most Promising Species of Ganoderma spp.

“…However, in another study, the polysaccharides from G. lucidum showed no cytotoxic effect on CML and HeLa cells [64]. Peng et al investigated the effect of one immunomodulatory peptide from G. microsporum on S. aureus methicyllin-resistant Staphylococcus aureus (MRSA) promoted expansion of myeloid-derived suppressor cells (MDSCs) to suppress T-cell proliferation and the peptide increased IL-6 and TNF-alpha levels and thus the author suggested that G. microsporum could be useful for periprosthetic joint infections induced by S. aureus [65]. Selected biological activities of terpenes from Ganoderma spp.…”