Extracellular Vesicle-Mediated Communication Within Host-Parasite Interactions

Extracellular vesicles (EVs) are small membrane-surrounded structures released by different kinds of cells (normal, diseased, and transformed cells) in vivo and in vitro that contain large amounts of important substances (such as lipids, proteins, metabolites, DNA, RNA, and non-coding RNA (ncRNA), including miRNA, lncRNA, tRNA, rRNA, snoRNA, and scaRNA) in an evolutionarily conserved manner. EVs, including exosomes, play a role in the transmission of information, and substances between cells that is increasingly being recognized as important. In some infectious diseases such as parasitic diseases, EVs have emerged as a ubiquitous mechanism for mediating communication during host-parasite interactions. EVs can enable multiple modes to transfer virulence factors and effector molecules from parasites to hosts, thereby regulating host gene expression, and immune responses and, consequently, mediating the pathogenic process, which has made us rethink our understanding of the host-parasite interface. Thus, here, we review the present findings regarding EVs (especially exosomes) and recognize the role of EVs in host-parasite interactions. We hope that a better understanding of the mechanisms of parasite-derived EVs may provide new insights for further diagnostic biomarker, vaccine, and therapeutic development

Anti-Inflammatory Protein of Schistosoma japonicum Directs the Differentiation of the WEHI-3B JCS Cells and Mouse Bone Marrow Cells to Macrophages

Sj16 is an anti-inflammatory protein identified from Schistosoma japonicum. Our previous studies showed that recombinant Sj16 (rSj16) could suppress host's inflammatory responses and inhibit macrophage maturation. In the present study, the effects of rSj16 on the differentiation of the murine myeloid leukemia WEHI-3B JCS cell line and on mouse hematopoiesis were investigated. Our data demonstrated that rSj16 expressed and purified from Escherichia coli could suppress the proliferation of the WEHI-3B JCS cells in a time- and concentration-dependent manner, while not affect the viability of the cells. Further studies indicated that rSj16 induced macrophage differentiation of the WEHI-3B JCS cells, and arrested the cell cycle in the G1/G0 and G2/M phases. The macrophage differentiation of the rSj16-treated WEHI-3B JCS cells was confirmed by their expression of macrophage specific antigen F4/80 and phagocytic activity. Furthermore, our results revealed that rSj16 biased the colony formation of mouse bone marrow cells towards macrophage linage

A cross-sectional study to assess the epidemiological situation and associated risk factors of dengue fever; knowledge, attitudes, and practices about dengue prevention in Khyber Pakhtunkhwa Province, Pakistan

BackgroundDengue fever has been responsible for around 12 countrywide large outbreaks in Pakistan, resulting in 286,262 morbidities and 1,108 deaths. Khyber Pakhtunkhwa (KP) is the most recently impacted province. This study aimed to investigate the molecular, epidemiological, and potential elements that contribute to increasing dengue transmission patterns, and knowledge, attitude, and practice (KAP) toward dengue in KP province.MethodThis cross-sectional community-based study was conducted (June-December, 2021) in two phases. Phase I involved the epidemiological (n = 5,242) and molecular analysis of DENV in 500 randomly collected blood samples of the 2021 dengue outbreak in KP. Phase II focused on assessing dengue-KAP levels in healthy communities (n = 14,745, aged >18 years), adopting a cross-sectional clustered multistage sampling in eight districts (dengue-hotspot vs. non-hotspot) of KP. Chi-square tests and logistic regression analysis were applied.ResultsPeshawar district had the highest dengue cases (60.0%) associated with the predominant co-circulation of DENV-2 (45.8%) and DENV-3 (50.4%) serotypes. A rise in cases was reported in October (41.8%) followed by September (27.9%) and August (14.4%; p < 0.001). Males (63.7%, p < 0.001) and individuals aged 16–30 years (37.0%, p < 0.001) were highly affected. General workers (18.0%), families with a monthly income of 10,000–20,000 Pak rupees (50.5%), unmarried (71.0%), uneducated (31%), families with higher human density (>10 individuals per household), and those (29.0%) who faced power outages for more than 7/24 h were the most affected. Moreover, co-morbidities like renal failure and bronchial asthma were associated with disease severity. A community survey on KAP revealed that an average of 74, 60, and 43% of the participants demonstrated good knowledge, attitudes, and dengue preventive practices, respectively.ConclusionMultiple poor socioeconomic elements are influencing dengue fever transmission in the province. Higher KAP levels may explain the low frequency of dengue in non-hotspot districts. Our study emphasizes the need for effective and long-term public health education, strengthened vector surveillance, and expanded laboratory capacity for better diagnosis and management of dengue cases to better predict the burden and seasonality of disease in the country

Preliminary expression profile of cytokines in brain tissue of BALB/c mice with Angiostrongylus cantonensis infection

BACKGROUND: Angiostrongylus cantonensis (A. cantonensis) infection can result in increased risk of eosinophilic meningitis. Accumulation of eosinophils and inflammation can result in the A. cantonensis infection playing an important role in brain tissue injury during this pathological process. However, underlying mechanisms regarding the transcriptomic responses during brain tissue injury caused by A. cantonensis infection are yet to be elucidated. This study is aimed at identifying some genomic and transcriptomic factors influencing the accumulation of eosinophils and inflammation in the mouse brain infected with A. cantonensis. METHODS: An infected mouse model was prepared based on our laboratory experimental process, and then the mouse brain RNA Libraries were constructed for deep Sequencing with Illumina Genome Analyzer. The raw data was processed with a bioinformatics’ pipeline including Refseq genes expression analysis using cufflinks, annotation and classification of RNAs, lncRNA prediction as well as analysis of co-expression network. The analysis of Refseq data provides the measure of the presence and prevalence of transcripts from known and previously unknown genes. RESULTS: This study showed that Cys-Cys (CC) type chemokines such as CCL2, CCL8, CCL1, CCL24, CCL11, CCL7, CCL12 and CCL5 were elevated significantly at the late phase of infection. The up-regulation of CCL2 indicated that the worm of A. cantonensis had migrated into the mouse brain at an early infection phase. CCL2 could be induced in the brain injury during migration and CCL2 might play a major role in the neuropathic pain caused by A. cantonensis infection. The up-regulated expression of IL-4, IL-5, IL-10, and IL-13 showed Th2 cell predominance in immunopathological reactions at late infection phase in response to infection by A. cantonensis. These different cytokines can modulate and inhibit each other and function as a network with the specific potential to drive brain eosinophilic inflammation. The increase of ATF-3 expression at 21 dpi suggested the injury of neuronal cells at late phase of infection. 1217 new potential lncRNA were candidates of interest for further research. CONCLUSIONS: These cytokine networks play an important role in the development of central nervous system inflammation caused by A. cantonensis infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-015-0939-6) contains supplementary material, which is available to authorized users

Exosomes Derived from Dendritic Cells Treated with Schistosoma japonicum Soluble Egg Antigen Attenuate DSS-Induced Colitis

Exosomes are 30–150 nm small membrane vesicles that are released into the extracellular medium via cells that function as a mode of intercellular communication. Dendritic cell (DC)-derived exosomes modulate immune responses and prevent the development of autoimmune diseases. Moreover, Schistosoma japonicum eggs show modulatory effects in a mouse model of colitis. Therefore, we hypothesized that exosomes derived from DCs treated with S. japonicum soluble eggs antigen (SEA; SEA-treated DC exosomes) would be useful for treating inflammatory bowel disease (IBD). Exosomes were purified from the supernatant of DCs treated or untreated with SEA and identified via transmission electron microscopy, western blotting and NanoSight. Acute colitis was induced via the administration of dextran sulfate sodium (DSS) in drinking water (5.0%, wt/vol). Treatment with exosomes was conducted via intraperitoneal injection (i.p.; 50 μg per mouse) from day 0 to day 6. Clinical scores were calculated based on weight loss, stool type, and bleeding. Colon length was measured as an indirect marker of inflammation, and colon macroscopic characteristics were determined. Body weight loss and the disease activity index of DSS-induced colitis mice decreased significantly following treatment with SEA-treated DC exosomes. Moreover, the colon lengths of SEA-treated DC exosomes treated colitis mice improved, and their mean colon macroscopic scores decreased. In addition, histologic examinations and histological scores showed that SEA-treated DC exosomes prevented colon damage in acute DSS-induced colitis mice. These results indicate that SEA-treated DC exosomes attenuate the severity of acute DSS-induced colitis mice more effectively than DC exosomes. The current work suggests that SEA-treated DC exosomes may be useful as a new approach to treat IBD

Genome of the rams horn snail Biomphalaria straminea : an obligate intermediate host of schistosomiasis

This work was supported by the Hong Kong Research Grant Council Collaborative Research Fund (C4015-20EF), General Research Fund (14100919), NSFC/RGC Joint Research Scheme (N_CUHK401/21), and The Chinese University of Hong Kong Direct Grant (4053433, 4053489). Y.Y., W.L.S., C.F.W., S.T.S.L., and Y.L. were supported by the Ph.D. studentships of The Chinese University of Hong Kong. A.H. is supported by a Biotechnology and Biological Sciences Research Council (BBSRC) David Phillips Fellowship (BB/N020146/1). T.B. is supported by a studentship from the Biotechnology and Biological Sciences Research Council-funded South West Biosciences Doctoral Training Partnership (BB/M009122/1). M.E.A.R. is supported by a Ph.D. studentship from the School of Biology and St Andrews University.Background: Schistosomiasis, or bilharzia, is a parasitic disease caused by trematode flatworms of the genus Schistosoma. Infection by Schistosoma mansoni in humans results when cercariae emerge into water from freshwater snails in the genus Biomphalaria and seek out and penetrate human skin. The snail Biomphalaria straminea is native to South America and is now also present in Central America and China, and represents a potential vector host for spreading schistosomiasis. To date, genomic information for the genus is restricted to the neotropical species Biomphalaria glabrata. This limits understanding of the biology and management of other schistosomiasis vectors, such as B. straminea. Findings: Using a combination of Illumina short‐read, 10X Genomics linked‐read, and Hi‐C sequencing data, our 1.005 Gb B. straminea genome assembly is of high contiguity, with a scaffold N50 of 25.3 Mb. Transcriptomes from adults were also obtained. Developmental homeobox genes, hormonal genes, and stress-response genes were identified, and repeat content was annotated (40.68% of genomic content). Comparisons with other mollusc genomes (including Gastropoda, Bivalvia, and Cephalopoda) revealed syntenic conservation, patterns of homeobox gene linkage indicative of evolutionary changes to gene clusters, expansion of heat shock protein genes, and the presence of sesquiterpenoid and cholesterol metabolic pathway genes in Gastropoda. In addition, hormone treatment together with RT-qPCR assay reveal a sesquiterpenoid hormone responsive system in B. straminea, illustrating that this renowned insect hormonal system is also present in the lophotrochozoan lineage. Conclusion: This study provides the first genome assembly for the snail B. straminea and offers an unprecedented opportunity to address a variety of phenomena related to snail vectors of schistosomiasis, as well as evolutionary and genomics questions related to molluscs more widely.Publisher PDFPeer reviewe

The transplant rejection response involves neutrophil and macrophage adhesion-mediated trogocytosis and is regulated by NFATc3

The anti-foreign tissue (transplant rejection) response, mediated by the immune system, has been the biggest obstacle to successful organ transplantation. There are still many enigmas regarding this process and some aspects of the underlying mechanisms driving the immune response against foreign tissues remain poorly understood. Here, we found that a large number of neutrophils and macrophages were attached to the graft during skin transplantation. Furthermore, both types of cells could autonomously adhere to and damage neonatal rat cardiomyocyte mass (NRCM) in vitro. We have demonstrated that Complement C3 and the receptor CR3 participated in neutrophils/macrophages-mediated adhesion and damage this foreign tissue (NRCM or skin grafts). We have provided direct evidence that the damage to these tissues occurs by a process referred to as trogocytosis, a damage mode that has never previously been reported to directly destroy grafts. We further demonstrated that this process can be regulated by NFAT, in particular, NFATc3. This study not only enriches an understanding of host-donor interaction in transplant rejection, but also provides new avenues for exploring the development of novel immunosuppressive drugs which prevent rejection during transplant therapy

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

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

Large-scale prediction of long non-coding RNA functions in a coding–non-coding gene co-expression network

Although accumulating evidence has provided insight into the various functions of long-non-coding RNAs (lncRNAs), the exact functions of the majority of such transcripts are still unknown. Here, we report the first computational annotation of lncRNA functions based on public microarray expression profiles. A coding–non-coding gene co-expression (CNC) network was constructed from re-annotated Affymetrix Mouse Genome Array data. Probable functions for altogether 340 lncRNAs were predicted based on topological or other network characteristics, such as module sharing, association with network hubs and combinations of co-expression and genomic adjacency. The functions annotated to the lncRNAs mainly involve organ or tissue development (e.g. neuron, eye and muscle development), cellular transport (e.g. neuronal transport and sodium ion, acid or lipid transport) or metabolic processes (e.g. involving macromolecules, phosphocreatine and tyrosine)