Follicular Helper T Cells Promote Liver Pathology in Mice during Schistosoma japonicum Infection

Chen, Xiaojun; Yang, Xiaowei; Li, Yong; Zhu, Jing; Zhou, Sha; Xu, Zhipeng; He, Lei; Xue, Xue; Zhang, Weiwei; Dong, Xiaoxiao; Wu, Henry; Li, Carrie J.; Hsu, Hui‐Chen; Kong, Wenjun; Liu, Feng; Tripathi, Prateek; Yu, Michelle S.; Chang, Jason Y. H.; Zhou, Liang; Su, Chuan

doi:10.1371/journal.ppat.1004097

Cited by 42 publications

(55 citation statements)

References 80 publications

(95 reference statements)

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“…11,12 In recent studies, it was reported that Th17/IL-17 and follicular helper T cells (Tfh)/IL-21 were correlated with severe pathology and subsequent fibrosis in schistosomiasis. 13,14 Down-regulation of Th17/IL-17 or Tfh/IL-21 could decrease granulomatous inflammation and ameliorate liver fibrosis. [15][16][17] During the chronic phase, the Th2 response is still predominant and modulated, but the granulomas are smaller than at earlier stages. The reason is that regulatory T cells play an important repressor role in the down-regulation of pathological immune responses at this stage.…”

Section: Introductionmentioning

confidence: 99%

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: Introductionmentioning

confidence: 99%

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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“…Are Tfh cells harmful to Trichinella? A previous study reported a role for Tfh cells in a Schistosoma japonicum infection model (29). That study found that when ICOSdeficient mice with impaired Tfh differentiation were infected with S. japonicum, amelioration of liver pathology was observed, and also that the adaptive transfer of Tfh cells into ICOS-deficient mice reestablished the liver pathology with enhanced cell accumulation in granulomas, indicating that Tfh cells are involved in the pathology of helminth infection.…”

Section: Discussionmentioning

confidence: 88%

Nonencapsulated Trichinella pseudospiralis Infection Impairs Follicular Helper T Cell Differentiation with Subclass-Selective Decreases in Antibody Responses

Asano

Srinontong

et al. 2016

Infect Immun

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cInfectious microorganisms often modify host immunity to escape from immune elimination. Trichinella is a unique nematode of the helminth family, whose members parasitize the muscle cells inside the host without robust eliminative reactions. There are several species of Trichinella; some develop in muscle cells that become encapsulated (e.g., Trichinella spiralis) and others in cells that do not encapsulate (e.g., Trichinella pseudospiralis). It has already been established that Trichinella infection affects host immune responses in several experimental immune diseases in animal models; however, most of those studies were done using T. spiralis infection. As host immune responses to T. spiralis and T. pseudospiralis infections have been reported to be different, it is necessary to clarify how T. pseudospiralis infection influences the host immune responses. In this study, we investigated the influence on host humoral immunity in T. pseudospiralis-infected mice. We demonstrated that T. pseudospiralis infection decreased antigen-specific IgG2a and IgG2b antibody (Ab) production in mice immunized with a model antigen. This selective decrease in gamma interferon (IFN-␥)-dependent Ab production was not due to a decrease in IFN-␥ production, and we instead found impaired follicular helper T (Tfh) cell differentiation. The affinity maturation of antigen-specific Ab tended to be delayed but was not significant in T. pseudospiralis-infected mice. We also observed that CD11b ؉ spleen cells in T. pseudospiralis-infected mice expressed CD206 and PD-L2, the phenotype of which was M2 macrophages with weak production of interleukin-6 (IL-6), possibly resulting in impaired Tfh differentiation. Taken together, our results indicate that nonencapsulated Trichinella infection induces selective dampening in humoral immunity with the suppression of Tfh differentiation.T richinella species are parasitic nematodes for many mammalian hosts, including humans (1). After the ingestion of muscle tissues contaminated with the muscle larval form of Trichinella, the larvae develop into adult worms by molting in the small intestine of the host. Female adult worms invade the intestinal tissue to release newborn larvae. Newborn larvae systemically migrate in the host body to striated muscle cells, resulting in survival for many years (2). Trichinella are thought to establish long-term parasitism by escaping elimination through alterations in host immune responses (3, 4). There are several species of Trichinella; some develop in muscle cells that become encapsulated (e.g., Trichinella spiralis and T. britovi) and others in cells that do not encapsulate (e.g., Trichinella pseudospiralis). Although both types of Trichinella survive in the host muscle tissues for long periods of time, the strategies for their survival may be different. Indeed, the infected host mounts an immune response to the infection with both types of Trichinella, but each immune response is different, possibly due to the different forms of immunomodulation shown by each Trichine...

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“…Although our previously published data documents that Tfh cells represent a key pathogenic player in schistosomiasis japonica, little is known about how Tfh cells promote the granuloma formation. Given that the granuloma is characterized by the eosinophil‐rich granulomatous lesions, we wondered whether Tfh cells promote the granuloma formation through recruiting the eosinophils into the liver during schistosome infection.…”

Section: Resultsmentioning

confidence: 95%

“…Given that the granuloma is characterized by the eosinophil‐rich granulomatous lesions, we wondered whether Tfh cells promote the granuloma formation through recruiting the eosinophils into the liver during schistosome infection. In ICOSL knockout (KO) mice, a widely used Tfh cell deficiency model, we showed a distinct reduction in the cellularity of granulomas surrounding single schistosome eggs after S japonicum infection (Figure A). Notably, the relative number of eosinophils in granulomas was substantially reduced in Tfh cell‐deficient mice (Figure B).…”

Section: Resultsmentioning

confidence: 98%

“…Single‐cell suspensions from spleen, mesenteric lymph nodes and liver were isolated in phosphate‐buffered saline (PBS) containing 1% foetal bovine serum as described previously . For CXCL12 + Tfh cell analysis, cells were stimulated for 6 hours in culture medium containing phorbol myristate acetate (PMA, 25 ng/mL; Sigma‐Aldrich), ionomycin (1 μg/mL; Sigma‐Aldrich) and monensin (Golgi Stop; 1 μg/mL; BD Biosciences).…”

Section: Methodsmentioning

confidence: 99%

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Follicular helper T cells recruit eosinophils into host liver by producing CXCL12 during Schistosoma japonicum infection

Chen

Wei

et al. 2020

J Cellular Molecular Medi

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Schistosomiasis affects at least 200 million people in tropical and subtropical areas. The major pathology of schistosomiasis is egg‐induced liver granuloma characterized by an eosinophil‐rich inflammatory infiltration around the eggs, which subsequently leads to hepatic fibrosis and circulatory impairment in host. However, the mechanisms how eosinophils are recruited into the liver, which are crucial for the better understanding of the mechanisms underlying granuloma formation and control of schistosomiasis, remain unclear. In this study, we showed that follicular helper T (Tfh) cells participate in recruitment of eosinophils into liver partially by producing CXCL12 during schistosome infection. Our findings uncovered a previously unappreciated role of Tfh cells in promotion of the development of liver granuloma in schistosomiasis, making Tfh‐CXCL12‐eosinophil axis a potential target for intervention of schistosomiasis.

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Follicular Helper T Cells Promote Liver Pathology in Mice during Schistosoma japonicum Infection

Cited by 42 publications

References 80 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

Nonencapsulated Trichinella pseudospiralis Infection Impairs Follicular Helper T Cell Differentiation with Subclass-Selective Decreases in Antibody Responses

Follicular helper T cells recruit eosinophils into host liver by producing CXCL12 during Schistosoma japonicum infection

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