Characteristics of IL-9 induced by Schistosoma japonicum infection in C57BL/6 mouse liver

Li, Lü; Xie, Hongyan; Wang, Mei; Qu, Jiale; Cha, Hefei; Yang, Quan; Feng, Yuanfa; Qi, Yanwei; Qiu, Huaina; Dong, Ning; Huang, Jun

doi:10.1038/s41598-017-02422-8

Cited by 23 publications

(20 citation statements)

References 28 publications

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“…More importantly, we found that the degree of liver fibrosis was also alleviated after neutralization of IL-9. This result was consistent with the findings of Li et al, 34 but the mechanisms of IL-9 pro-fibrosis remain unknown. As the granuloma matures, fibroblasts, which lead to production of extracellular matrix and collagen fibres, were recruited at the outer zone of the granuloma, resulting in fibrosis.…”

Section: Discussionsupporting

confidence: 93%

Interleukin‐9 blockage reduces early hepatic granuloma formation and fibrosis during Schistosoma japonicum infection in mice

Zhan¹,

Ma²,

Jiang³

et al. 2019

Immunology

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Summary Hepatic fibrosis induced by schistosomes is regulated by a complex network of cytokines. T helper type 9 (Th9) cells are a new type of effector T helper cells, which mainly secrete the specific cytokine interleukin‐9 (IL‐9). Interleukin‐9 has been shown to contribute to liver fibrosis in patients with chronic hepatitis B and in a mouse model due to carbon tetrachloride. However, the role of IL‐9 in schistosomiasis fibrosis remains unknown. In this study, we investigated the roles of IL‐9 in schistosomiasis through in vivo and in vitro studies. The in vivo studies found that neutralization of IL‐9 reduced liver granulomatous inflammation and collagen deposition around parasite eggs. The in vitro studies found that the treatment of primary hepatic stellate cells with IL‐9 induced a significant increase of collagen and α‐smooth‐muscle actin. Moreover, we also described the dynamics and relevance of IL‐9 and IL‐4 in mice infected with Schistosoma japonicum. We found that IL‐9 might appear more quickly and at higher levels than IL‐4. Hence, our findings indicated that IL‐9 might play a role in regulating hepatic fibrosis in early‐stage schistosomiasis and become a promising approach for regulating hepatic fibrosis caused by S. japonicum.

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Section: Discussionsupporting

confidence: 93%

Interleukin‐9 blockage reduces early hepatic granuloma formation and fibrosis during Schistosoma japonicum infection in mice

Zhan¹,

Ma²,

Jiang³

et al. 2019

Immunology

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“…Moreover, dynamic changes of Th9, IL-9, and PU.1 levels were consistent with hepatic egg granulomatous inflammation (101). In agreement with these studies, Li et al additionally showed that anti-IL-9 monoclonal antibody treatment significantly inhibits S. japonicum-induced hepatic granulomatous and fibrosing inflammation (102). The above findings indicate that Th9 cells may be involved in immunopathogenesis in murine schistosomiasis.…”

Section: Th9 Cells and Egg-induced Hepatic Granulomatous And Fibrosissupporting

confidence: 63%

T Lymphocyte-Mediated Liver Immunopathology of Schistosomiasis

et al. 2020

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The parasitic worms, Schistosoma mansoni and Schistosoma japonicum, reside in the mesenteric veins, where they release eggs that induce a dramatic granulomatous response in the liver and intestines. Subsequently, infection may further develop into significant fibrosis and portal hypertension. Over the past several years, uncovering the mechanism of immunopathology in schistosomiasis has become a major research objective. It is known that T lymphocytes, especially CD4 + T cells, are essential for immune responses against Schistosoma species. However, obtaining a clear understanding of how T lymphocytes regulate the pathological process is proving to be a daunting challenge. To date, CD4 + T cell subsets have been classified into several distinct T helper (Th) phenotypes including Th1, Th2, Th17, T follicular helper cells (Tfh), Th9, and regulatory T cells (Tregs). In the case of schistosomiasis, the granulomatous inflammation and the chronic liver pathology are critically regulated by the Th1/Th2 responses. Animal studies suggest that there is a moderate Th1 response to parasite antigens during the acute stage, but then, egg-derived antigens induce a sustained and dominant Th2 response that mediates granuloma formation and liver fibrosis. In addition, the newly discovered Th17 cells also play a critical role in the hepatic immunopathology of schistosomiasis. Within the liver, Tregs are recruited to hepatic granulomas and exert an immunosuppressive role to limit the granulomatous inflammation and fibrosis. Moreover, recent studies have shown that Tfh and Th9 cells might also promote liver granulomas and fibrogenesis in the murine schistosomiasis. Thus, during infection, T-cell subsets undergo complicated cross-talk with antigen presenting cells that then defines their various roles in the local microenvironment for regulating the pathological progression of schistosomiasis. This current review summarizes a vast body of literature to elucidate the contribution of T lymphocytes and their associated cytokines in the immunopathology of schistosomiasis.

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“… 56 Follicular helper T cells and Th9 cells have also been implicated in promoting egg-induced hepatic granulomas and fibrosis. 57 , 58 Thus, Th2 immunity functions like a two-edged sword, on one hand protecting the host against excessive granulomatous inflammation, and on the other, causing host immune-dependent liver damage. A balance between Th1 and Th2 responses may therefore be necessary to prevent severe pathology.…”

Section: What We Have Learnt From Experimental Animal Studiesmentioning

confidence: 99%

<p>Current Understanding of Immunity Against Schistosomiasis: Impact on Vaccine and Drug Development</p>

Molehin

2020

RRTM

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Schistosomiasis is a neglected tropical disease inflicting significant morbidity in humans worldwide. The disease is caused by infections with a parasitic trematode belonging to the genus Schistosoma . Over 250 million people are currently infected globally, with an estimated disability-adjusted life-years of 1.9 million attributed to the disease. Current understanding, based on several immunological studies using experimental and human models of schistosomiasis, reveals that complex immune mechanisms play off each other in the acquisition of immune resistance to infection/reinfection. Nevertheless, the precise characteristics of these responses, the specific antigens against which they are elicited, and how these responses are intricately regulated are still being investigated. What is apparent is that immunity to schistosome infections develops slowly and over a prolonged period of time, augmented by the death of adult worms occurring naturally or by praziquantel therapy. In this review, aspects of immunity to schistosomiasis, host–parasite interactions and their impact on schistosomiasis vaccine development are discussed.

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Characteristics of IL-9 induced by Schistosoma japonicum infection in C57BL/6 mouse liver

Cited by 23 publications

References 28 publications

Interleukin‐9 blockage reduces early hepatic granuloma formation and fibrosis during Schistosoma japonicum infection in mice

Interleukin‐9 blockage reduces early hepatic granuloma formation and fibrosis during Schistosoma japonicum infection in mice

T Lymphocyte-Mediated Liver Immunopathology of Schistosomiasis

<p>Current Understanding of Immunity Against Schistosomiasis: Impact on Vaccine and Drug Development</p>

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