Frontiers | Cellular and Molecular Basis in Parasitic Diseases Control: Research Trends

Editorial13 April 2022

Editorial: Cellular and Molecular Basis in Parasitic Diseases Control: Research Trends

Jianbing Mu, Jun Cao, Gaoqian Fengand Qingfeng Zhang

Significant progress in parasite disease control has been made recently by applying novel tools and methodologies developed in genomic, epigenomic, proteomics, and metabolomics research.The research topic aimed to introduce some of the key developments and challenges of the field, focusing on parasite-induced immune response, genetic and epigenetic regulation mechanisms, and potential therapeutics. This Research Topic comprises 41 papers, including three reviews and 38 original research articles, spans topics that cover parasite biology, host pathology, epidemiology, and prevention and control programs. Together, this research topic brings important new data and provides a broad and diverse overview of cellular and molecular basis in parasitic diseases control. The collected articles are timely and address important questions in the field with overwhelmingly positive feedback (total 534,000 views and over 1,000 views for most articles). We hope this research topic will promote further investigations and drive the field toward better control for parasitic diseases.

All authors listed have made a substantial and intellectual contribution to the work and approved it for publication.

1,521 views

A Putative Plasmodium RNA-Binding Protein Plays a Critical Role in Female Gamete Fertility and Parasite Transmission to the Mosquito Vector

ORIGINAL RESEARCH

4 April 2022

A Putative Plasmodium RNA-Binding Protein Plays a Critical Role in Female Gamete Fertility and Parasite Transmission to the Mosquito Vector

Sudhir Kumar, 5 more and Stefan H.I. Kappe

Plasmodium falciparum sexual stages called gametocytes are critical for parasite transmission from the human host to the mosquito host. Mature gametocytes generate fertile gametes upon activation inside the mosquito midgut. While a number of parasite genes have been described that are critical for gametogenesis and fertility, no parasite gene was shown yet to have a unique function in female (macro) gametes of P. falciparum. The genome of P. falciparum encodes numerous RNA-binding proteins. We identified a novel putative RNA-binding domain protein, which we named Macrogamete-Contributed Factor Essential for Transmission (MaCFET), that is expressed in the asexual and sexual stages. Pf macfet¯ parasites that carry a deletion of MaCFET develop normally as asexual stages, indicating that PfMaCFET function is not essential for the asexual proliferation of the parasite in vitro. Furthermore, Pf macfet¯ male and female gametocytes develop normally and undergo activation to release microgametes and macrogametes. However, by utilizing genetic crosses we demonstrate that Pf macfet¯ parasites suffer a complete female-specific defect in successful fertilization. Therefore, Pf MaCFET is a critical female-contributed factor for transmission to the mosquito. Based on its putative RNA-binding properties, PfMaCFET might be in involved in the regulation of mRNAs that encode female-specific functions during fertilization or post fertilization.

4,260 views

17 citations

ORIGINAL RESEARCH

20 January 2022

Properties and Roles of γδT Cells in Plasmodium yoelii nigeriensis NSM Infected C57BL/6 Mice

Hongyan Xie, 12 more and Jun Huang

5,339 views

10 citations

Molecular Mechanisms of Clonorchis sinensis-Host Interactions and Implications for Vaccine Development

REVIEW

18 January 2022

Molecular Mechanisms of Clonorchis sinensis-Host Interactions and Implications for Vaccine Development

Stephane Koda, 2 more and Chao Yan

8,148 views

21 citations

Functional Characterization of 17 Protein Serine/Threonine Phosphatases in Toxoplasma gondii Using CRISPR-Cas9 System

ORIGINAL RESEARCH

10 January 2022

Functional Characterization of 17 Protein Serine/Threonine Phosphatases in Toxoplasma gondii Using CRISPR-Cas9 System

Qin-Li Liang, 7 more and Jin-Lei Wang

Protein serine/threonine phosphatases (PSPs), found in various plants and protozoa, are involved in the regulation of various biological processes. However, very little is known about the role of PSPs in the pathogenicity of the apicomplexan protozoan Toxoplasma gondii. Herein, the subcellular localization of 17 PSPs (PP5, PP7, EFPP, SLP, PPM3F, PPM4, PPM5A, PPM5B, PPM6, PPM8, PPM9, PPM12, PPM14, PPM18, CTD1, CTD2 and CTD3) was examined by 6×HA tagging of endogenous genes in C-terminal. The PSPs were detected in the cytoplasm (PP5, EFPP, PPM8 and CTD2), dense granules (SLP), nucleus (PPM4 and PPM9), inner membrane complex (PPM12), basal complex (CTD3), and apical pole (PP7). The remaining PSPs exhibited low or undetectable level of expression. To characterize the contribution of these genes to the infectivity of T. gondii, knock-out (KO) strains of type Ⅰ RH strain deficient in the 17 psp genes and KO type Ⅱ Pru strain of deficient in pp7 and slp genes were constructed. The pathogenicity of individual RHΔpsp mutants was characterized in vitro using plaque, egress, and intracellular replication assays, and mouse infection, while pathogenicity of PruΔpp7 and PruΔslp mutant strains was evaluated by examining the parasite lytic cycle in vitro and assessment of brain cyst burden in mice. No significant differences were observed between 16 RHΔpsp strains and wild-type (WT) RH strain. However, RHΔpp7 exhibited significantly lower invasion efficiency and parasitophorous vacuole formation in vitro, and low virulence in mice compared to other RHΔpsp and WT strains. In addition, PruΔpp7 exhibited marked attenuation of virulence and significant reduction in the brain cyst burden in mice compared with PruΔslp and WT strains, suggesting the key role of PP7 in the virulence of T. gondii. Comparative transcriptomic profiling of the 17 psp genes showed that they may play different roles in the pathogenesis of different genotypes or life cycle stages of T. gondii. These findings provide new insight into the role of PSPs in the pathogenesis of T. gondii.

3,889 views

22 citations

ORIGINAL RESEARCH

10 January 2022

PfAP2-EXP2, an Essential Transcription Factor for the Intraerythrocytic Development of Plasmodium falciparum

Xiaomin Shang, 7 more and Mei Jiang

4,754 views

16 citations

Multipurpose Drugs Active Against Both Plasmodium spp. and Microorganisms: Potential Application for New Drug Development

REVIEW

24 December 2021

Multipurpose Drugs Active Against Both Plasmodium spp. and Microorganisms: Potential Application for New Drug Development

Takuro Endo, 2 more and Tetsuya Furuya

7,839 views

8 citations

ORIGINAL RESEARCH

4 January 2022

RNA Secondary Structurome Revealed Distinct Thermoregulation in Plasmodium falciparum

Yanwei Qi, 7 more and Xinhua Wang

4,066 views

11 citations

Proteomics Investigations of Potential Protein Biomarkers in Sera of Rabbits Infected With Schistosoma japonicum

ORIGINAL RESEARCH

22 December 2021

Proteomics Investigations of Potential Protein Biomarkers in Sera of Rabbits Infected With Schistosoma japonicum

Nian-Nian Bi, 5 more and Kun Yang

4,237 views

18 citations

ORIGINAL RESEARCH

13 December 2021

Glycogenes in Oncofetal Chondroitin Sulfate Biosynthesis are Differently Expressed and Correlated With Immune Response in Placenta and Colorectal Cancer

Zi-Yi Wu, 8 more and Wei-Hua Jia

Oncofetal chondroitin sulfate expression plays an important role in the development of tumors and the pathogenesis of pregnancy malaria. However, the biosynthesis and functions of these chondroitin sulfates, particularly the tissue-specific regulation either in tumors or placenta, have not been fully elucidated. Here, by examining the glycogenes availability in chondroitin sulfate biosynthesis such as xylosytransferase, chondroitin synthase, sulfotransferase, and epimerase, the conserved or differential CS glycosylation in normal, colorectal cancer (CRC) and placenta tissue were predicted. We found that the expression of 7 chondroitin sulfate biosynthetic enzymes, including B4GALT7, B3GALT6, B3GAT3, CHSY3, CHSY1, CHPF, and CHPF2, were significantly increased, while 4 other enzymes (XYLT1, CHST7, CHST15, UST) were decreased in the colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ) patients. In the human placenta, where the distinct chondroitin sulfate is specifically bound with VAR2CSA on Plasmodium parasite-infected RBC, 8 chondroitin sulfate biosynthesis enzymes (CSGALNACT1, CSGALNACT2, CHSY3, CHSY1, CHPF, DSE, CHST11, and CHST3) were significantly higher than the normal colon tissue. The similarly up-regulated chondroitin synthases (CHSY1, CHSY3, CHPF) in both cancer tissue and human placenta indicate an important role of the proteoglycan CS chains length for Plasmodium falciparum VAR2CSA protein binding. Interestingly, 12 highly expressed chondroitin sulfate enzymes were significantly correlated to worse outcomes (prognosis) in both COAD and READ. Furthermore, we showed that the levels of chondroitin sulfate enzymes are significantly correlated with the expression of immuno-regulators and immune infiltration levels in CRCs and placenta, and involved in multiple essential pathways, such as extracellular matrix organization, epithelial-mesenchymal transition, and cell adhesion. Our study provides novel insights into the oncofetal chondroitin sulfate biosynthesis regulation and identifies promising targets and biomarkers of immunotherapy for CRC and pregnancy malaria.

7,785 views

26 citations

ORIGINAL RESEARCH

6 December 2021

Identification of the Recombinant Plasmodium vivax Surface-Related Antigen as a Possible Immune Evasion Factor Against Human Splenic Fibroblasts by Targeting ITGB1

Haitian Fu, 8 more and Yang Cheng

Plasmodium vivax-infected erythrocytes can enter the spleen and evade spleen clearance to establish chronic infections. However, the mechanism underlying P. vivax immune evasion in the spleen is still unclear. Human splenic fibroblasts (HSF), also known as barrier cells, play an essential role in immune function of spleen. A hypothesis holds that P. vivax-infected erythrocytes induce spleen structural remodeling to form barrier cells. Subsequently, these infected erythrocytes can selectively cytoadhere to these barrier cells to escape spleen clearance. In this work, P. vivax surface-related antigen (PvSRA), an exported protein on infected erythrocyte membrane, was found to be able to bind with HSF. Considering the above hypothesis, we speculated that PvSRA might be involved in P. vivax immune evasion by changing HSF cell performance. To investigate this speculation, RNA sequencing, protein microarray and bioinformatics analysis technologies were applied, and in vitro validations were further performed. The results showed that PvSRA attracted HSF migration and interacted with HSF by targeting ITGB1 along with changes in HSF cell performance, such as focal adhesion, extracellular matrix, actin cytoskeleton and cell cycle. This study indicated that PvSRA might indeed participate in the immune evasion of P. vivax in the spleen by changing HSF function through PvSRA-ITGB1 axis.

14,648 views

4 citations

Therapeutic Effect of Schistosoma japonicum Cystatin on Atherosclerotic Renal Damage

ORIGINAL RESEARCH

25 November 2021

Therapeutic Effect of Schistosoma japonicum Cystatin on Atherosclerotic Renal Damage

Huijuan Yang, 12 more and Xiaodi Yang

Atherosclerosis is a chronic inflammation of the arterial vessel wall driven by lipid metabolism disorders. Although helminth infection and their derivatives have been identified to attenuate the chronic inflammatory diseases, the immunomodulatory effect of recombinant Schistosoma japonicum cystatin (rSj-Cys) on metabolic diseases and atherosclerosis has not been reported. In this study, we investigated the therapeutic efficacy of rSj-Cys on atherosclerotic renal damage and explored the related immunological mechanism. The results demonstrated that treatment with rSj-Cys significantly reduced body weight gain, hyperlipidemia and atherosclerosis induced by the high-fat diet in apoE−/− mice. The treatment of rSj-Cys also significantly improved kidney functions through promoting macrophage polarization from M1 to M2, therefore inhibiting M1 macrophage-induced inflammation. The possible mechanism underlying the regulatory effect of rSj-Cys on reducing atherosclerosis and atherosclerotic renal damage is that rSj-Cys stimulates Treg and M2 macrophage polarization that produce regulatory cytokines, such as IL-10 and TGF-β. The therapeutic effect of rSj-Cys on atherosclerotic renal damage possibly through inhibiting the activation of TLR2/Myd88 signaling pathway. The results in this study provide evidences for the first time that Schistosoma-derived cystatin could be developed as a therapeutic agent to treat lipid metabolism disorder and atherosclerosis that threats million’s lives around the world.

3,741 views

18 citations

ORIGINAL RESEARCH

16 November 2021

Development of a Recombinase Polymerase Amplification Assay for Schistosomiasis Japonica Diagnosis in the Experimental Mice and Domestic Goats

Qinghong Guo, 12 more and Yang Hong

3,152 views

19 citations

Bacillus subtilis Attenuates Hepatic and Intestinal Injuries and Modulates Gut Microbiota and Gene Expression Profiles in Mice Infected with Schistosoma japonicum

ORIGINAL RESEARCH

16 November 2021

Bacillus subtilis Attenuates Hepatic and Intestinal Injuries and Modulates Gut Microbiota and Gene Expression Profiles in Mice Infected with Schistosoma japonicum

Datao Lin, 8 more and Xi Sun

Parasitic infection can induce pathological injuries and impact the gut microbiota diversity and composition of the host. Bacillus subtilis (B. subtilis) is a nonpathogenic and noninvasive probiotic bacterium for humans and other animals, playing an important role in improving the host immune system’s ability to respond to intestinal and liver diseases and modulating gut microbiota. However, whether B. subtilis can impact biological functions in Schistosoma japonicum-infected mice is unclear. This study used oral administration of (OA) B. subtilis to treat mice infected with S. japonicum. We evaluated changes in the gut microbiota of infected mice using 16S rRNA gene sequencing and differentially expressed gene profiles using transcriptome sequencing after OA B. subtilis. We found that OA B. subtilis significantly attenuated hepatic and intestinal pathological injuries in infected mice. The gut microbiota of mice were significantly altered after Schistosoma japonicum infection, while OA B. subtilis remodel the diversity and composition of gut microbiomes of infected mice. We found that the Schistosoma japonicum-infected mice with OA B. subtilis had an overabundance of the most prevalent bacterial genera, including Bacteroides, Enterococcus, Lactobacillus, Blautia, Lachnoclostridium, Ruminiclostridium, and Enterobacter. Transcriptomic analysis of intestinal tissues revealed that OA B. subtilis shaped the intestinal microenvironment of the host responding to S. japonicum infection. Differentially expressed genes (DEGs) were classified into KEGG pathways between Schistosoma japonicum-infected mice and those without included cell adhesion molecules (CAMs), intestinal immune network for IgA production, hematopoietic cell lineage, Fc epsilon RI signaling pathway, Th1 and Th2 cell differentiation, Th17 cell differentiation, calcium signaling pathway, Fc gamma R-mediated phagocytosis, chemokine signaling pathway, phospholipase D signaling pathway, NF-kappa B signaling pathway, B cell receptor signaling pathway, pancreatic secretion, and phagosome. In conclusion, our findings showed that OA B. subtilis alleviates pathological injuries and regulates gene expression, implying that B. subtilis supplementation may be a potential therapeutic strategy for schistosomiasis. Our study may highlight the value of probiotics as a beneficial supplementary therapy during human schistosomiasis, but further studies are needed.

6,388 views

20 citations

ORIGINAL RESEARCH

11 November 2021

Malaria Parasites Hijack Host Receptors From Exosomes to Capture Lipoproteins

Naoyuki Iso-o, 7 more and Kiyoshi Kita

6,257 views

7 citations

ORIGINAL RESEARCH

11 November 2021

Mining Anti-Inflammation Molecules From Nippostrongylus brasiliensis-Derived Products Through the Metabolomics Approach

Yuying Chen, 7 more and Junhong Wang

4,393 views

10 citations

ORIGINAL RESEARCH

9 November 2021

Analysis of Intestinal Microflora and Metabolites From Mice With DSS-Induced IBD Treated With Schistosoma Soluble Egg Antigen

Tianyu Zhu, 7 more and Yuzheng Huang

This study aimed to analyze the changes in intestinal flora and metabolites in the intestinal contents of mice with IBD to preliminarily clarify the mechanism of action of SEA on IBD, thus, laying a research foundation for the subsequent treatment of IBD. A total of 40 ICR mice were divided into 4 groups: control, SEA 50 μg, dextran sulfate sodium salt (DSS), and SEA 50 μg + DSS. The overall state of the animals was observed continuously during modeling. The colonic length was measured after 10 days of modeling. The degree of colonic inflammation was observed by hematoxylin and eosin staining. 16srRNA and liquid chromatography–mass spectrometry sequencing techniques were used to determine the abundance of bacteria and metabolites in the intestinal contents of mice in the DSS and SEA 50 μg + DSS groups, and the differences were further analyzed. Results: After SEA intervention, the disease activity index score of mice with IBD decreased and the colon shortening was reduced. Microscopically, the lymphocyte aggregation, glandular atrophy, goblet cell disappearance, and colonic inflammation were less in the SEA 50 μg + DSS group than in the DSS group (P < 0.0001). After SEA intervention, the abundance of beneficial bacteria prevotellaceAE_UCG-001 was upregulated, while the abundance of the harmful bacteria Helicobacter, Lachnoclostridium, and Enterococcus was downregulated in the intestinal tract of mice with IBD. The intestinal metabolite analysis showed that SEA intervention decreased the intestinal contents of glycerophospholipids (lysophosphatidylcholine, lysophosphatidylethanolamine, phatidylcholine, and phatidylethanolamine) and carboxylic acids (L-alloisoleucine and L-glutamate), whereas increased bile acids and their derivatives (3B,7A,12a-trihydroxy-5A-cholanoic acid and 3A,4B,12a-trihydroxy-5b-cholanoic acid). Combined microbiota–metabolite analysis revealed a correlation between these differential microbiota and differential metabolites. At the same time, the changes in the contents of metabolites and differential metabolites in the two groups also correlated with the abundance of the gut microbiome. The study showed that SEA reduced DSS-induced inflammation in IBD and improved the symptoms of IBD in mice through the combined regulation of intestinal flora and intestinal metabolism. It suggested a potential possibility for the use of SEA in treating and regulating intestinal flora and metabolism in patients with IBD.

5,281 views

27 citations