Different miRNAs are involved in the life cycles of Schistosoma japonicum. The aim of this study was to examine the expression profile of miRNAs in individual S. japonicum of different sex before and after pairing (18 and 24 dpi). The majority of differential expressed miRNAs were highly abundant at 14 dpi, except for sja-miR-125b and sja-miR-3505, in both male and female. Moreover, it was estimated that sja-miR-125b and sja-miR-3505 might be related to laying eggs. sja-miR-2a-5p and sja-miR-3484-5p were expressed at 14 dpi in males and were significantly clustered in DNA topoisomerase III, Rap guanine nucleotide exchange factor 1 and L-serine/L-threonine ammonia-lyase. Target genes of sja-miR-2d-5p, sja-miR-31- 5p and sja-miR-125a, which were expressed at 14 dpi in males but particularly females, were clustered in kelch-like protein 12, fructose-bisphosphate aldolase, class I, and heat shock protein 90 kDa beta. Predicted target genes of sja-miR-3483-3p (expressed at 28 dpi in females but not in males) were clustered in 26S proteasome regulatory subunit N1, ATPdependent RNA helicase DDX17. Predicted target genes of sja-miR-219-5p, which were differentially expressed at 28 dpi in females but particularly males, were clustered in DNA excision repair protein ERCC-6, protein phosphatase 1D, and ATPase family AAA domaincontaining protein 3A/B. Moreover, at 28 dpi, eight miRNAs were significantly up-regulated in females compared to males. The predicted target genes of these miRNAs were significantly clustered in heat shock protein 90 kDa beta, 26S proteasome regulatory subunit N1, and protein arginine N-methyltransferase 1. To sum up, differentially expressed miRNAs may have an essential role and provide necessary information on clarifying this trematode's growth, development, maturation, and infection ability to mammalian hosts in its complex life cycle, and may be helpful for developing new drug targets and vaccine candidates for schistosomiasis.
Matched MeSH terms: Schistosoma japonicum/genetics*; Schistosoma japonicum/growth & development
Schistosoma malayensis n. sp., a member of the Schistosoma japonicum complex is described from Rattus muelleri in Peninsular Malaysia and 2 strains are characterized. The only morphological differences noted among adults from natural hosts were that S. malayensis are in general smaller than S. mekongi and S. japonicum. But these differences may be the result of host-induced variations and therefore are of little taxonomic value. To minimize the effects of host-induced variations, adult worms recovered from laboratory mice with similar worm burdens at 50-56 days postinfection were compared. These comparisons revealed only minor morphometric differences among these 3 species. Schistosoma malayensis eggs from naturally and experimentally infected hosts are most similar to those of S. mekongi, with eggs of both species being, in general, smaller than those of S. japonicum. The egg index for S. malayensis is usually higher than for S. japonicum and lower than for S. mekongi. Differences were noted in the developmental rates in mice for 2 isolates of S. malayensis, S. mekongi, and S. japonicum (Philippine strain), but relatively large differences observed between isolates of S. malayensis indicate that, in this case, the developmental rate is not a useful taxonomic character. Schistosoma malayensis is erected principally on the basis of differences, reported elsewhere, in the life histories and in the electrophoretic migration patterns of isoenzymes of adult worms as compared to S. mekongi and S. japonicum. These comparisons indicate that S. malayensis is more closely related to S. mekongi than to S. japonicum.
Electrophoretically-detected allozyme variation is described in strains of Schistosoma japonicum (4 Philippine strains), S. mekongi (Laos), and an undescribed anthropophilic S. japonicum-like schistosome from Peninsular Malaysia. Result, together with those reported previously for 8 other strains (S. japonicum, China, Formosa, Japan, Philippines; S. mekongi, 2 substrains; Malaysian schistosome, 2 strains) permit a composite genetic characterization of 15 strains of Asian schistosomes at 9-18 presumptive loci. The proportion of polymorphic loci (P) and the mean heterozygosity per locus (H) were zero in all strains. Although this was expected for strains that had been in laboratory culture for up to 50 years, we expected to detect variation in strains based on 10-50 recently field-collected infected snails. We expected S. japonicum to be as variable as S. mansoni (P = 0.13 (0-0.33), H = 0.04, 18 loci, 22 strains) as it is believed to reproduce sexually, has an evolutionary history of several million years, inhabits a wide geographic range, coevolved with a genetically variable intermediate snail host, and has a diversity of mammalian hosts. No differences were detected between the 5 S. japonicum strains from Leyte and Luzon (Philippines), between the 3 S. mekongi strains, or between the 3 Malaysian schistosome strains; these groups and the remaining S. japonicum strains representing Mindoro (Philippines), China, Formosa, and Japan each have distinctive multilocus electromorphic patterns. Nei's genetic distances (D) were calculated to estimate interstrain and interspecific divergence. Interstrain genetic distances in S. japonicum averaged greater than 0.3; much higher than those reported previously for S. mansoni (D = 0.06, D(max) = 0.24). S. japonicum (Mindoro) was moderately differentiated from the Leyte-Luzon strains (D = 0.29, 12 loci). Estimates of the S. japonicum China-Philippine distance (D greater than 0.4, 11 loci) are high for conspecific populations and further studies of the still poorly characterized Chinese parasite may reveal that these are, in fact, separate species. S. japonicum is shown to be only distantly related to S. mekongi and the Malaysian schistosome (D greater than 1); the latter is closely related to, but genetically quite distinct from, S. mekongi (D = 0.61 +/- 0.275, 11 loci) and warrants recognition as a new species. The medical significance of the isogenic nature of the Asian schistosome strains and their evolutionary divergence are discussed.
Laboratory experiments were carried out to study the susceptibility of snail vectors to Oriental anthropophilic Schistosoma. Oncomelania hupensis hupensis was readily infected with the local strain of Schistosoma japonicum (Chinese strain), and also infected with S. japonicum (Philippines strain). O.h. quadrasi was only susceptible to its S. japonicum (Philippines strain). The Oncomelania races were refractory to S. mekongi, S. japonicum-like species (Malaysian strain). Tricula aperta (beta race) was readily infected with S. mekongi, S. sinensium and S. japonicum-like species from Malaysia, but not S. japonicum. T. bollingi was susceptible to S. sinensium and S. mekongi. Robertsiella kaporensis was only susceptible to the local strain, S. japonicum-like species from Malaysia. Geographical isolation may be the cause of these differences in compatibility between the snail vectors and the schistosome parasites.
Recent electrophoretic data have indicated that Schistosoma japonicum in mainland China may be a species complex, with the existence of a cryptic species being predicted from the analysis of schistosome populations from Sichuan province. To investigate the Sichuan form of S. japonicum, 4.9 kbp of mitochondrial DNA from each of three samples of the parasite from China (two from Sichuan and one from Hunan) and one from Sorsogon in the Philippines were amplified, sequenced and characterized. The sequence data were compared with those from the related South-east Asian species of S. mekongi (Khong Island, Laos) and S. mlayensis (Baling, Malaysia) and that from S. japonicm from Anhui (China). At both the nucleotide and amino-acid levels, the variation among the five S. japonicum samples was limited (< 1%). This was consistent with the conclusions drawn from previous molecular studies, in which minimal variation among S. japonicum populations was also detected. In contrast, S. mekongi and S. malayensis, species recognized as separate but closely related, differ from each other by about 10%, and each differs by 25%-26% from S. japonicum. Phylogenetic trees provided a graphic representation of these differences, showing all S. japonicum sequences to be very tightly clustered and distant from S. mekongi and S. malayensis, the last two being clearly distinct from each other. The results thus indicate no significant intra-specific genetic variation among S. japonicum samples collected from different geographical areas and do not support the idea of a distinct form in Sichuan.
Schistosomiasis was discovered in Malaysia in 1975 in an autopsy case. Since 1975 autopsies, surveys, and resurveys have been carried out to identify animal hosts, snail intermediate hosts, and reservoir hosts. Seroepidemiologic tests involving enzyme-linked immunosorbent and circumoval precipitin methods have been used to determine the true incidence and prevalence of this protean disease among the Orang Aslis (aborigines) in Malaysia. With the use of better epidemiologic and parasitologic tools, more cases of schistosomiasis are being reported.
Schistosomiasis is a neglected tropical disease that affects more than 200 million people worldwide. The main disease-causing agents, Schistosoma japonicum, S. mansoni and S. haematobium, are blood flukes that have complex life cycles involving a snail intermediate host. In Asia, S. japonicum causes hepatointestinal disease (schistosomiasis japonica) and is challenging to control due to a broad distribution of its snail hosts and range of animal reservoir hosts. In China, extensive efforts have been underway to control this parasite, but genetic variability in S. japonicum populations could represent an obstacle to eliminating schistosomiasis japonica. Although a draft genome sequence is available for S. japonicum, there has been no previous study of molecular variation in this parasite on a genome-wide scale. In this study, we conducted the first deep genomic exploration of seven S. japonicum populations from mainland China, constructed phylogenies using mitochondrial and nuclear genomic data sets, and established considerable variation between some of the populations in genes inferred to be linked to key cellular processes and/or pathogen-host interactions. Based on the findings from this study, we propose that verifying intraspecific conservation in vaccine or drug target candidates is an important first step toward developing effective vaccines and chemotherapies against schistosomiasis.
Neutrophils contribute to the pathological processes of a number of inflammatory disorders, including rheumatoid arthritis, sepsis and cystic fibrosis. Neutrophils also play prominent roles in schistosomiasis japonica liver fibrosis, being central mediators of inflammation following granuloma formation. In this study, we investigated the interaction between Schistosoma japonicum eggs and neutrophils, and the effect of eggs on the inflammatory phenotype of neutrophils. Our results showed significant upregulated expression of pro-inflammatory cytokines (IL-1α, IL-1β and IL-8) and chemokines (CCL3, CCL4 and CXCL2) in neutrophils after 4 h in vitro stimulation with S. japonicum eggs. Furthermore, mitochondrial DNA was released by stimulated neutrophils, and induced the production of matrix metalloproteinase 9 (MMP-9), a protease involved in inflammation and associated tissue destruction. We also found that intact live eggs and isolated soluble egg antigen (SEA) triggered the release of neutrophil extracellular traps (NETs), but, unlike those reported in bacterial or fungal infection, NETs did not kill schistosome eggs in vitro. Together these show that S. japonicum eggs can induce the inflammatory phenotype of neutrophils, and further our understanding of the host-parasite interplay that takes place within the in vivo microenvironment of schistosome-induced granuloma. These findings represent novel findings in a metazoan parasite, and confirm characteristics of NETs that have until now, only been observed in response to protozoan pathogens.
Two groups of three rabbits each were infected with 250 cercariae of the Baling and Koyan strain of Schistosoma malayensis. Changes induced by both strains included periportal hepatocellular necrosis and fibrosis. Vascular changes such as portal phlebitis and thrombophlebitis and varying degrees of pericholangitis were also present. Amyloid deposition was noted. A comparative study of the changes induced in rabbits by S. malayensis, S. mekongi and S. japonicum showed that the hepatic lesions induced by the Baling strain of S. malayensis were similar to that induced by S. japonicum, and were more severe than that induced by S. mekongi or the Koyan strain.
Three cases of schistosomiasis in 2 Filipinos and one Chinese in Sabah are reported. Diagnosis was based on incidental histological findings of Schistosoma japonicum-like ova in the liver and rectal biopsies. As these 3 patients are immigrants to Sabah, it is assumed that they are imported cases, and that Sabah has been free of the disease from 1970 to 1977.
For hepatic schistosomiasis the egg-induced granulomatous response and the development of extensive fibrosis are the main pathologies. We used a Schistosoma japonicum-infected mouse model to characterise the multi-cellular pathways associated with the recovery from hepatic fibrosis following clearance of the infection with the anti-schistosomal drug, praziquantel. In the recovering liver splenomegaly, granuloma density and liver fibrosis were all reduced. Inflammatory cell infiltration into the liver was evident, and the numbers of neutrophils, eosinophils and macrophages were significantly decreased. Transcriptomic analysis revealed the up-regulation of fatty acid metabolism genes and the identification of Peroxisome proliferator activated receptor alpha as the upstream regulator of liver recovery. The aryl hydrocarbon receptor signalling pathway which regulates xenobiotic metabolism was also differentially up-regulated. These findings provide a better understanding of the mechanisms associated with the regression of hepatic schistosomiasis.
The first living patient with a Schistosoma japonicum-type infection who presented with the nephrotic syndrome is reported in detail. It is not clear whether the nephrotic syndrome was due to the schistosome infection or to the deposition of hepatitis B antigen and antibody complexes. This is the tenth case of schistosomiasis reported from aborigines in Malaysia and a sylvatic source of infection is suggested.
In hepatic schistosomiasis, pathology arises when schistosome eggs become lodged in the host liver, evoking an interleukin 4 (IL-4)- and IL-13-mediated dominant CD4(+) Th2 immune response. This response leads to the development of granulomas and fibrosis, with eosinophils, neutrophils, macrophages, hepatic stellate cells, and lymphocytes all identified as major cellular contributors to these events. This review outlines the cellular and molecular mechanisms of hepatic schistosomiasis, with an emphasis on the major cellular components and their release of chemokines. The differences between Schistosoma mansoni- and Schistosoma japonicum-induced hepatic granuloma are also discussed. This comprehensive overview of the processes associated with hepatic schistosomiasis may provide new insights into improved treatment for both schistosomiasis and other granulofibrotic diseases.
Schistosomiasis in Southeast Asia, caused by Schistosoma japonicum, Schistosoma mekongi and Schistosoma japonicum-like, have been reported from six different countries. The S. japonicum infections are highly prevalent in the Philippines with Oncomelania hupensis quadrasi as the vector snail, and in localized areas in Indonesia with O.h. lindoensis as the snail vector. The S. mekongi infections are recent discovery in the Lower Mekong Basin in Laos and Kampuchea, with Tricula aperta as the vector snail. The S. japonicum-like infections are found as isolated cases diagnosed by the finding of S. japonicum-like eggs in the faeces, rectal biopsy, tissue biopsy or at necropsy in Thailand and Malaysia. The control measures of schistosomiasis have been implemented in the Philippines and Indonesia, while further research studies are being conducted in Thailand and Malaysia.