From Inflammation to Fibrosis: Novel Insights into the Roles of High Mobility Group Protein Box 1 in Schistosome-Induced Liver Damage

Abstract

Schistosomiasis is a chronic helminthic disease of both humans and animals and the second most prevalent parasitic disease after malaria. Through a complex migration process, schistosome eggs trapped in the liver can lead to the formation of granulomas and subsequent schistosome-induced liver damage, which results in high mortality and morbidity. Although praziquantel can eliminate mature worms and prevent egg deposition, effective drugs to reverse schistosome-induced liver damage are scarce. High mobility group box 1 (HMGB1) is a multifunctional cytokine contributing to liver injury, inflammation, and immune responses in schistosomiasis by binding to cell-surface Toll-like receptors and receptors for advanced glycation end products. HMGB1 is increased in the serum of patients with schistosomiasis and enables hepatic stellate cells to adopt a proliferative myofibroblast-like phenotype, which is crucial to schistosome-induced granuloma formation. Inhibition of HMGB1 was found to generate protective responses against fibrotic diseases in animal models. Clinically, HMGB1 presents a potential target for treatment of the chronic sequelae of schistosomiasis. Here, the pivotal role of HMGB1 in granuloma formation and schistosome-induced liver damage, as well the potential of HMGB1 as a therapeutic target, are discussed.

Tropical infections as occupational diseases among young volunteers in social projects

“…A schistosomiasis screening for antibodies and preferably followed by the more sensitive up-converting phosphor lateral ow circulating anodic antigen (UPC-LF CAA) test should be encouraged after freshwater contact (Anonymous last updated version 10/2017) (Casacuberta-Partal et al 2020a). In high-endemic areas serology should be analysed 12 weeks after return (Anonymous 2017), (Kapaun 2004) to detect potentially active infestations with low burden of schistosomiasis pathogen after staying abroad, as travelers may be asymptomatic on rst presentation (Casacuberta-Partal et al 2020b) and infections need to be treated early in order to prevent long-term complications in the case of chronic schistosomiasis, as liver brosis (Zhong et al 2022), bladder cancer (Efared et al 2022)and other chronic in ammations (Musaigwa et al 2022).…”

Multifunctional Roles of MicroRNAs in Schistosomiasis

“…A single-sex infected female worm is characterized by incomplete development with stunting and an immature reproductive system, as the vitelline glands that produce the eggshell precursors and nutrients for the egg are not fully developed ( LoVerde et al, 2009 ; Zhong et al, 2022b ). Hence, single-sex infected worms do not cause serious damage to the host because underdeveloped worms cannot produce normal eggs ( Zhong et al, 2022a ). Han et al (2020) employed Solexa deep-sequencing technology to identify 36 differentially expressed miRNAs between normal and underdeveloped female worms at 25 dpi, of which 20 were up-regulated and 16 were down-regulated in mated females.…”

“…Advanced liver disease induced by S. mansoni and S. japonicum , which is often irreversible without prompt medical treatment, leads to the high morbidity and mortality rates of schistosomiasis ( Zhong et al, 2022a ). Elucidation of the molecular mechanisms that mediate the progression of schistosomiasis has been a primary research goal for several decades.…”

“…Each mature female worm can lay hundreds or thousands of eggs per day (depending on species), of which about one-third to one-half become trapped in the host tissues, accounting for the primary pathology of schistosomiasis ( Cheever et al, 1994 ; Zhong et al, 2022a ). Egg-induced granuloma formation and tissue fibrosis due to the host immune response are the main causes of the high morbidity and mortality of schistosomiasis ( Llanwarne and Helmby, 2021 ).…”

“…Most of the remaining eggs are excreted in urine or feces. Then, miracidia hatch from the eggs in fresh water and seek a suitable snail as an intermediate host to complete and repeat the life cycle ( Nation et al, 2020 ; Zhong et al, 2022a ). Hence, schistosome eggs are also responsible for the occurrence and spread of schistosomiasis.…”