Mechanisms of Resistance to Schistosoma japonicum Infection in Microtus fortis, the Natural Non-permissive Host

Shen, Jia; Xiang, Suoyu; Peng, Mei; Zhou, Zhijun; Wu, Zhongdao

doi:10.3389/fmicb.2020.02092

Cited by 8 publications

(8 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although many studies have been done on parasitic protozoa, there are still a lot of enigmas surrounding the remarkable differences in the susceptibility among hosts toward helminth infections. The resistance of M. fortis against schistosome infection is a typical example 44 . In the last few decades, although a large number of studies have been undertaken to explore the mechanism behind this efficient resistance in M. fortis , the underlying mechanisms remain poorly understood.…”

Section: Discussionmentioning

confidence: 99%

Macrophage-mediated trogocytosis contributes to destroying human schistosomes in a non-susceptible rodent host, Microtus fortis

Shen,

Zhao,

Peng

et al. 2023

Cell Discov

Self Cite

View full text Add to dashboard Cite

Schistosoma parasites, causing schistosomiasis, exhibit typical host specificity in host preference. Many mammals, including humans, are susceptible to infection, while the widely distributed rodent, Microtus fortis, exhibits natural anti-schistosome characteristics. The mechanisms of host susceptibility remain poorly understood. Comparison of schistosome infection in M. fortis with the infection in laboratory mice (highly sensitive to infection) offers a good model system to investigate these mechanisms and to gain an insight into host specificity. In this study, we showed that large numbers of leukocytes attach to the surface of human schistosomes in M. fortis but not in mice. Single-cell RNA-sequencing analyses revealed that macrophages might be involved in the cell adhesion, and we further demonstrated that M. fortis macrophages could be mediated to attach and kill schistosomula with dependence on Complement component 3 (C3) and Complement receptor 3 (CR3). Importantly, we provided direct evidence that M. fortis macrophages could destroy schistosomula by trogocytosis, a previously undescribed mode for killing helminths. This process was regulated by Ca2+/NFAT signaling. These findings not only elucidate a novel anti-schistosome mechanism in M. fortis but also provide a better understanding of host parasite interactions, host specificity and the potential generation of novel strategies for schistosomiasis control.

show abstract

Section: Discussionmentioning

confidence: 99%

Macrophage-mediated trogocytosis contributes to destroying human schistosomes in a non-susceptible rodent host, Microtus fortis

Shen,

Zhao,

Peng

et al. 2023

Cell Discov

Self Cite

View full text Add to dashboard Cite

show abstract

“…Based on the differences in resistance to Schistosoma , definitive hosts are classified into nonpermissive hosts and permissive hosts. Nonpermissive hosts with stronger resistance to Schistosoma include Microtus fortis , rats and buffalo ( Yang et al., 2013 ; Shen et al., 2020 ), in which Schistosoma fails to develop to sexual maturity. Permissive hosts exhibiting less resistance to Schistosoma include mice, goats and humans, where the adult worms lay eggs and consequently develop hepatic lesions characterized by egg granulomas ( Yang et al., 2013 ).…”

Section: Main Textmentioning

confidence: 99%

“…Immune factors include humoral immunity components, cytokines and immune cells. At the humoral immunity level, the resistance of M. fortis to S. japonicum is dependent on serum albumin and IgG3 helping to eliminate worms ( Jiang et al., 2010 ; Li et al., 2013 ), whereas in rats, this resistance depends on IgG2a and IgE ( Shen et al., 2020 ). The application of purified albumin from M. fortis infecting mice exerts significant effects on worm load reduction, suggesting a promising target for therapy ( Jiang et al., 2010 ; Li et al., 2013 ).…”

Section: Main Textmentioning

confidence: 99%

“…The outcomes of parasite-host adaptation are generally closely related to host genetic backgrounds, yet summaries in this field are lacking. In this article, the host adaptation of parasites and the potential mechanisms remarkably influenced by host genetic backgrounds are reviewed ( Shen et al., 2020 ). It is expected that this review will provide new insights for the in-depth understanding of parasite-host adaptation as well as strategies to prevent and control parasitic infection in the future.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Host genetic backgrounds: the key to determining parasite-host adaptation

Zhang

Tang

et al. 2023

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Parasitic diseases pose a significant threat to global public health, particularly in developing countries. Host genetic factors play a crucial role in determining susceptibility and resistance to infection. Recent advances in molecular and biological technologies have enabled significant breakthroughs in understanding the impact of host genes on parasite adaptation. In this comprehensive review, we analyze the host genetic factors that influence parasite adaptation, including hormones, nitric oxide, immune cells, cytokine gene polymorphisms, parasite-specific receptors, and metabolites. We also establish an interactive network to better illustrate the complex relationship between host genetic factors and parasite-host adaptation. Additionally, we discuss future directions and collaborative research priorities in the parasite-host adaptation field, including investigating the impact of host genes on the microbiome, developing more sophisticated models, identifying and characterizing parasite-specific receptors, utilizing patient-derived sera as diagnostic and therapeutic tools, and developing novel treatments and management strategies targeting specific host genetic factors. This review highlights the need for a comprehensive and systematic approach to investigating the underlying mechanisms of parasite-host adaptation, which requires interdisciplinary collaborations among biologists, geneticists, immunologists, and clinicians. By deepening our understanding of the complex interactions between host genetics and parasite adaptation, we can develop more effective and targeted interventions to prevent and treat parasitic diseases. Overall, this review provides a valuable resource for researchers and clinicians working in the parasitology field and offers insights into the future directions of this critical research area.

show abstract

“…Schistosomiasis is a disease caused by Schistosoma parasites in the human body. It is estimated that at least 229 million people required preventive treatment in 2018 ( 1 ). Schistosoma japonicum ( S. japonicum ) is the main epidemic Schistosoma in China.…”

Section: Introductionmentioning

confidence: 99%

Ikzf2 Regulates the Development of ICOS+ Th Cells to Mediate Immune Response in the Spleen of S. japonicum-Infected C57BL/6 Mice

et al. 2021

View full text Add to dashboard Cite

BackgroundTh cells (helper T cells) have multiple functions in Schistosoma japonicum (S. japonicum) infection. Inducible co-stimulator (ICOS) is induced and expressed in activated T lymphocytes, which enhances the development of B cells and antibody production through the ICOS/ICOSL pathway. It remains unclear about the role and possible regulating mechanism of ICOS+ Th cells in the spleen of S. japonicum-infected C57BL/6 mice.MethodsC57BL/6 mice were infected with cercariae of S. japonicum through the abdomen. The expression of ICOS, activation markers, and the cytokine production on CD4+ ICOS+ Th cells were detected by flow cytometry (FCM) and quantitative real-time PCR (qRT-PCR). Moreover, the differentially expressed gene data of ICOS+ and ICOS− Th cells from the spleen of infected mice were obtained by mRNA sequencing. Besides, Western blot and chromatin immunoprecipitation (ChIP) were used to explore the role of Ikzf2 on ICOS expression.ResultsAfter S. japonicum infection, the expression of ICOS molecules gradually increased in splenic lymphocytes, especially in Th cells (P < 0.01). Compared with ICOS− Th cells, more ICOS+ Th cells expressed CD69, CD25, CXCR5, and CD40L (P < 0.05), while less of them expressed CD62L (P < 0.05). Also, ICOS+ Th cells expressed more cytokines, such as IFN-γ, IL-4, IL-10, IL-2, and IL-21 (P < 0.05). RNA sequencing results showed that many transcription factors were increased significantly in ICOS+ Th cells, especially Ikzf2 (P < 0.05). And then, the expression of Ikzf2 was verified to be significantly increased and mainly located in the nuclear of ICOS+ Th cells. Finally, ChIP experiments and dual-luciferase reporter assay confirmed that Ikzf2 could directly bind to the ICOS promoter in Th cells.ConclusionIn this study, ICOS+ Th cells were found to play an important role in S. japonicum infection to induce immune response in the spleen of C57BL/6 mice. Additionally, Ikzf2 was found to be one important transcription factor that could regulate the expression of ICOS in the spleen of S. japonicum-infected C57BL/6 mice.

show abstract

Mechanisms of Resistance to Schistosoma japonicum Infection in Microtus fortis, the Natural Non-permissive Host

Cited by 8 publications

References 68 publications

Macrophage-mediated trogocytosis contributes to destroying human schistosomes in a non-susceptible rodent host, Microtus fortis

Macrophage-mediated trogocytosis contributes to destroying human schistosomes in a non-susceptible rodent host, Microtus fortis

Host genetic backgrounds: the key to determining parasite-host adaptation

Ikzf2 Regulates the Development of ICOS+ Th Cells to Mediate Immune Response in the Spleen of S. japonicum-Infected C57BL/6 Mice

Contact Info

Product

Resources

About