ROS generation by Schistosome eggs boost hepatic pathology

Saptaparna Dasgupta, Bennett University

Schistosomiasis is a disregarded public health tropical disease. The most serious disease is largely attributable to the grain produced by eggs and subsequent fibrosis in the host liver. This may lead to portal hypertension or even the death of the host. Host disease is most commonly observed, schistosome eggs produce M2-rich granulomas, which are very important in maintaining granulomas and eventual fibrosis. These M2-macrophages play an integral role. Reactive oxygen (ROS) species strongly activated during infection generated by macrophages are disseminated massively surrounding eggs deposited in the liver, facilitating differentiation of M2 macrophage. It remains, however, to be clarified during Schistosoma japonicum infection if ROS is produced by schistosome eggs to further differentiate M2 by macrophage and the underlying potential processes.

Schistosomiasis:

The schistosomiasis of ~200 million individuals, particularly in (sub)tropic regions, is a neglected parasite poverty disease, leading to a huge health burden and considerable morbidity. Parasite eggs are trapped in the host’s liver and cause hepatic granulomas and fibrosis during Schistosoma japonicum or the infection of S. mansoni, leading to serious damage to the liver and even death of the host. Significant ROS accumulates in granulomas around hepatic schistosomiasis in eggs caught by the hepatic. However, the fact whether schistosome eggs induce ROS generation and how ROS supports hepatic disease in the host remains unclear.

Role of macrophage in schistosomiasis:

The introduction, maintenance, and resolution of chronic granulomatous inflammation depending on their effector phenotypes are known to be regulated by macrophages in schistosome infections. It’s one of the most significant cell types in hepatic granuloma, and it’s involved in both innate and adaptive immunity. When responding to a variety of stimulations the macrophages are activated and polarized in functional terms to either M1 or M2. M1 macrophages are found to be schistosomula cytotoxic and also contribute to hepatic fibrosis prevention. Macrophages create significant levels of ROS, as professional phagocytes, as their main instrument against invading pathogens. They are one of the major cell sources of ROS generation during hepatic fibrosis.

How was the study conducted?

The study by Yu et al. 2021 was performed on mouse animal models, and all studies were carried out in complete compliance with the Experimental Animal Administration Regulations. The Animal Center of Nanjing Medical University bought Specific pathogen-free (SPF) male 8-week-old male BALB/c mice (Nanjing, China). All the mice were raised in an SPF breeding facility under normal circumstances. For semi-quantitative examination of hepatic fibrosis, the liver slices were stained with the Masson’s Trichrome staining kit (Sigma-Aldrich). Followed by which, the ROS generation was measured in the mouse livers. Several analyses such as the serum ALT/AST, flow cytometry analysis, western blotting, and statistical analysis were performed.

Findings of the study:

Infection with Schistosoma japonicum produces granulomatous inflammation and fibrosis in the liver of the host. Mice infected with S. Japonicum had significant liver immunopathology, as well as gastrointestinal inflammation. In mice, the buildup of reactive oxygen species (ROS) contributes to hepatic immunopathology. Macrophages are well-known for their ability to generate a high quantity of reactive oxygen species (ROS) during hepatic inflammation and fibrosis caused by alcohol, lipid buildup, endotoxins, and viral infections. On hepatic schistosomiasis, no comparable information is known. During infection, schistosome eggs have been shown to enhance M2 macrophage development and generate M2-rich granulomas. It’s unclear if ROS generation stimulation is required for M2 macrophage differentiation caused by Schistosoma japonicum eggs.

Significance of the study:

Pathogens cause the host to produce a large amount of ROS. Significant levels of ROS develop in granulomas around liver-trapped eggs during hepatic schistosomiasis. The specific mechanisms by which ROS regulate granulomatous inflammation to induce fibrosis to become a focus of research. Increased ROS function as second messengers in macrophages and promote fibrosis, according to previous research. Our findings point to a previously unknown immunological function for ROS in increasing M2 macrophage differentiation and Th2 responses in hepatic schistosomiasis, which results in liver damage. In conclusion, our findings reveal that ROS buildup in the liver of Schistosoma japonicum infected mice leads to hepatic immunopathology and that schistosome eggs cause ROS production to enhance M2 macrophage development.

Also read: Inborn errors of immunity & corresponding protein interactions

Reference:

1. Yu, Y., Wang, J., Wang, X., Gu, P., Lei, Z., Tang, R., Wei, C., Xu, L., Wang, C., Chen, Y., Pu, Y., Qi, X., Yu, B., Chen, X., Zhu, J., Li, Y., Zhang, Z., Zhou, S., & Su, C. (2021). Schistosome eggs stimulate reactive oxygen species production to enhance M2 macrophage differentiation and promote hepatic pathology in schistosomiasis. PLOS Neglected Tropical Diseases, 15(8), e0009696. https://doi.org/10.1371/journal.pntd.0009696

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Author info:

Saptaparna Dasgupta, currently a B. Tech 3^rd year student, pursuing Biotechnology, is a diligent student and determined in terms of her career goals. Being a budding biotechnologist, she is open to all research fields of her course and passionate about knowledge. She is focused and constantly tries to improve her writing skills, also a project enthusiast and is fond of gaining hands-on experience in laboratories. She believes that all hard works and effort pay off eventually and follows this as the motto of her life.