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Schistosoma japonicum extracellular vesicle miRNA cargo regulates host macrophage functions facilitating parasitism.

ABSTRACT: Schistosome infection persists for decades. Parasites are in close contact with host peripheral blood immune cells, yet little is known about the regulatory interactions between parasites and these immune cells. Here, we report that extracellular vesicles (EVs) released from Schistosoma japonicum are taken up primarily by macrophages and other host peripheral blood immune cells and their miRNA cargo transferred into recipient cells. Uptake of S. japonicum EV miR-125b and bantam miRNAs into host cells increased macrophage proliferation and TNF-? production by regulating the corresponding targets including Pros1, Fam212b, and Clmp. Mice infected with S. japonicum exhibit an increased population of monocytes and elevated levels of TNF-?. Reduction of host monocytes and TNF-? level in S. japonicum infected mice led to a significant reduction in worm and egg burden and pathology. Overall, we demonstrate that S. japonicum EV miRNAs can regulate host macrophages illustrating parasite modulation of the host immune response to facilitate parasite survival. Our findings provide valuable insights into the schistosome-host interaction which may help to develop novel intervention strategies against schistosomiasis.

SUBMITTER: Liu J

PROVIDER: S-EPMC6548406 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Schistosoma japonicum extracellular vesicle miRNA cargo regulates host macrophage functions facilitating parasitism.

Liu Juntao J Zhu Lihui L Wang Jianbin J Qiu Lin L Chen Yongjun Y Davis Richard E RE Cheng Guofeng G

PLoS pathogens 20190604 6

Schistosome infection persists for decades. Parasites are in close contact with host peripheral blood immune cells, yet little is known about the regulatory interactions between parasites and these immune cells. Here, we report that extracellular vesicles (EVs) released from Schistosoma japonicum are taken up primarily by macrophages and other host peripheral blood immune cells and their miRNA cargo transferred into recipient cells. Uptake of S. japonicum EV miR-125b and bantam miRNAs into host ...[more]

PMID: 31163079

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Project description:Recently, we and others have illustrated that extracellular vesicles (EVs) have the potential to support hematopoietic stem and progenitor cell (HSPC) expansion; however, the mechanism and processes responsible for the intercellular communication by EVs are still unknown. In the current study, we investigate whether primary human bone marrow derived mesenchymal stromal cells (BMSC) EVs isolated from two different origins, fetal (fEV) and adult (aEV) tissue, can increase the relative low number of HSPCs found in umbilical cord blood (UCB) and which EV-derived components are responsible for ex vivo HSPC expansion. Interestingly, aEVs but and to a lesser extent fEVs, showed supportive ex vivo expansion capacity of UCB-HSPCs. Taking advantage of the two BMSC sources with different supportive effects, we analyzed the EV cargo and investigated how gene expression is modulated in HSPCs after incubation with aEVs and fEVs. Proteomics analyses of the protein cargo composition of the supportive aEV versus the less-supportive fEV identified 90% of the Top100 exosome proteins present in the ExoCarta database. Gene Ontology (GO) analyses illustrated that the proteins overrepresented in aEVs were annotated to oxidation-reduction process, mitochondrial ATP synthesis coupled proton transport, or protein folding. In contrast, the proteins overrepresented in fEVs were annotated to extracellular matrix organization positive regulation of cell migration or transforming growth factor beta receptor (TGFBR) signaling pathway. Small RNA sequencing identified different molecular signatures between aEVs and fEVs. Interestingly, the microRNA cluster miR-99b/let-7e/miR-125a, previously identified to increase the number of HSPCs by targeting multiple pro-apoptotic genes, was highly and significantly enriched in aEVs. Although we identified significant differences in the supportive effects of aEVs and fEVs, RNAseq analyses of the 24hrs treated HSPCs indicated that a limited set of genes was differentially regulated when compared to cells that were treated with cytokines only. Together, our study provides novel insights into the complex biological role of EVs and illustrates that aEVs and fEVs differentially support ex vivo expansion capacity of UCB-HSPCs. Together opening new means for the application of EVs in the discovery of therapeutics for more efficient ex vivo HSPC expansion.

Project description:BackgroundCo-parasitism is a frequent occurrence in impoverished communities in the tropics resulting in a considerable disease burden. While there are extensive reports of intestinal helminthiases, including schistosomiasis japonica, the occurrence and extent of diseases caused by intestinal protozoa (IP) have yet to be investigated in depth in the Philippines. We present a detailed analysis of polyparasitism in a rural community of Northern Samar, focusing on co-infections of IP with Schistosoma japonicum.MethodsA descriptive cross sectional study was carried out in 2015 across 18 barangays (villages) endemic for S. japonicum in Northern Samar, the Philippines to assess the burden of human schistosomiasis and IP infections. Faecal samples collected from 412 participants from the 18 barangays were included in the final molecular analysis. A multiplex quantitative PCR assay was developed and used for the detection of Blastocystis spp., Entamoeba histolytica, Cryptosporidium spp. and Giardia duodenalis in stool samples. The findings were combined with previous results of droplet digital PCR diagnosis of individuals from the same 18 barangays infected with S. japonicum determined using the same stool samples for analysis.ResultsMean age of the study participants was 40.3 years (95% CI: 38.8-41.8) with 53% (n = 218) being males. Prevalence of S. japonicum (74.5%) and Blastocystis spp. (58.7%) was significantly higher compared to other infections, with E. histolytica having the lowest prevalence (12.1%). A majority of individuals were infected with more than one parasite with two infections being most common (n = 175, 42.5%). The prevalence of individuals with two parasites was significantly higher than all others with 27.9% (n = 115) subjects harbouring a single parasite species. Of individuals with two infections, S. japonicum and Blastocystis spp. were the most common combination (n = 110, 62.9%). Examining age within the population, 58.5% (n = 38) of school-aged children and 60.1% (n = 14) of women of child bearing age harboured at least two parasite species.ConclusionsThe study revealed that polyparasitism with IP infections and schistosomiasis japonica is highly prevalent in individuals in Northern Samar which likely contributes to the significant public health and socio-economic burden suffered by this population. More generally, the findings are of relevance when considering implementation of integrated control strategies for intestinal parasites.

Dataset Information

Schistosoma japonicum extracellular vesicle miRNA cargo regulates host macrophage functions facilitating parasitism.

Publications

Schistosoma japonicum extracellular vesicle miRNA cargo regulates host macrophage functions facilitating parasitism.

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