Toll-like receptor-2 regulates macrophage polarization induced by excretory-secretory antigens from Schistosoma japonicum eggs and promotes liver pathology in murine schistosomiasis

• Published in: PLoS neglected tropical diseases 2018-12, Vol.12 (12), p.e0007000-e0007000
• Main Authors: Gong, Wenci, Huang, Fengjuan, Sun, Lei, Yu, Aiping, Zhang, Xiaofan, Xu, Yuxin, Shen, Yujuan, Cao, Jianping
• Format: Article
• Language: English
• Subjects: Animals; Antigens; Antigens, Helminth - genetics; Antigens, Helminth - metabolism; Biology; Biology and Life Sciences; Causes of; Cell Polarity; Chemokines; Cytokines; Dendritic cells; Development and progression; Disease control; Disease prevention; DNA; Eggs; Female; Fibrosis; Gene expression; Genetic aspects; Genotype & phenotype; Granuloma; Granulomas; Helminth Proteins - genetics; Helminth Proteins - metabolism; Humans; Hypertension; Immunology; Infections; Inflammation; Kinases; Laboratory animals; Ligands; Liver; Liver - metabolism; Liver - parasitology; Liver - pathology; Lymphocytes; Lymphocytes T; Macrophages; Macrophages - cytology; Macrophages - metabolism; MAP kinase; Medicine and Health Sciences; Metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Molecular modelling; MyD88 protein; NF-κB protein; Nucleotide sequence; Ovum - metabolism; Parasites; Parasitic diseases; Pathogenesis; Pathogens; Pathology; Pattern recognition; PCR; Physiological aspects; Polarization; Proteins; Rabbits; Receptors; Research and Analysis Methods; Schistosoma japonicum; Schistosoma japonicum - genetics; Schistosoma japonicum - metabolism; Schistosomiasis; Schistosomiasis japonica - parasitology; Schistosomiasis japonica - pathology; Schistosomiasis japonica - physiopathology; Signal Transduction; TLR2 protein; Toll-like receptors; Toll-Like Receptors - genetics; Toll-Like Receptors - metabolism; Tropical diseases
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0007000

Schistosomiasis is endemic to many regions of the world and affects approximately 200 million people. Conventional adaptive T cell responses are considered to be the primary contributors to the pathogenesis of Schistosoma japonicum infection, leading to liver granuloma and fibrosis. However, the functional polarization of macrophages and the associated underlying molecular mechanisms during the pathogenesis of schistosomiasis remains unknown. In the present study, we found that excretory-secretory (ES) antigens derived from S. japonicum eggs can activate macrophages, which exhibit an M2b polarization. Furthermore, ES antigen-induced M2b polarization was found to be dependent on enhanced NF-κB signaling mediated by the MyD88/MAPK pathway in a TLR2-dependent manner. In addition, the cytokine profile of the liver macrophages from wild-type-infected mice are quite distinct from those found in TLR2 knockout-infected mice by quantitative PCR analysis. More importantly, the size of granuloma and the severity of the fibrosis in the livers of TLR2-/- mice were significantly reduced compared to that in WT mice. Our findings reveal a novel role for M2b polarization in the pathogenesis of schistosome infection.