- Clonorchis sinensis excretory-secretory products regulate migration and invasion in cholangiocarcinoma cells via extracellular signal-regulated kinase 1/2/nuclear factor-κB-dependent matrix metalloproteinase-9 expression. [Journal Article]
- IJInt J Parasitol 2016 Dec 02
- Matrix metalloproteinase-9 (MMP-9) plays an important role in the invasion and metastasis of various types of cancer cells. We have previously reported that excretory-secretory products (ESPs) from C...
Matrix metalloproteinase-9 (MMP-9) plays an important role in the invasion and metastasis of various types of cancer cells. We have previously reported that excretory-secretory products (ESPs) from Clonorchis sinensis increases MMP-9 expression. However, the regulatory mechanisms through which MMP-9 expression affects cholangiocarcinoma development remain unclear. In the current study, we examined the potential role of ESPs in regulating the migration and invasion of various cholangiocarcinoma cell lines. We demonstrated that ESPs significantly induced MMP-9 expression and activity in a concentration-dependent manner. Reporter gene and chromatin immunoprecipitation assays showed that ESPs induced MMP-9 expression by enhancing the activity of nuclear factorkappa B (NF-κB). Moreover, ESPs induced the degradation and phosphorylation of IκBα and stimulated NF-κB p65 nuclear translocation, which was regulated by extracellular signal-regulated kinase 1/2. Taken together, our findings indicated that the ESP-dependent enhancement of MMP-9 activity and subsequent induction of IκBα and NF-κB activities may contribute to the progression of cholangiocarcinoma.
- Modelling the consequences of targeted selective treatment strategies on performance and emergence of anthelmintic resistance amongst grazing calves. [Journal Article]
- IJInt J Parasitol Drugs Drug Resist 2016 Nov 16; 6(3):258-271
- The development of anthelmintic resistance by helminths can be slowed by maintaining refugia on pasture or in untreated hosts. Targeted selective treatments (TST) may achieve this through the treatme...
The development of anthelmintic resistance by helminths can be slowed by maintaining refugia on pasture or in untreated hosts. Targeted selective treatments (TST) may achieve this through the treatment only of individuals that would benefit most from anthelmintic, according to certain criteria. However TST consequences on cattle are uncertain, mainly due to difficulties of comparison between alternative strategies. We developed a mathematical model to compare: 1) the most 'beneficial' indicator for treatment selection and 2) the method of selection of calves exposed to Ostertagia ostertagi, i.e. treating a fixed percentage of the population with the lowest (or highest) indicator values versus treating individuals who exceed (or are below) a given indicator threshold. The indicators evaluated were average daily gain (ADG), faecal egg counts (FEC), plasma pepsinogen, combined FEC and plasma pepsinogen, versus random selection of individuals. Treatment success was assessed in terms of benefit per R (BPR), the ratio of average benefit in weight gain to change in frequency of resistance alleles R (relative to an untreated population). The optimal indicator in terms of BPR for fixed percentages of calves treated was plasma pepsinogen and the worst ADG; in the latter case treatment was applied to some individuals who were not in need of treatment. The reverse was found when calves were treated according to threshold criteria, with ADG being the best target indicator for treatment. This was also the most beneficial strategy overall, with a significantly higher BPR value than any other strategy, but its degree of success depended on the chosen threshold of the indicator. The study shows strong support for TST, with all strategies showing improvements on calves treated selectively, compared with whole-herd treatment at 3, 8, 13 weeks post-turnout. The developed model appeared capable of assessing the consequences of other TST strategies on calf populations.
- Trematodes with a reproductive division of labour: heterophyids also have a soldier caste and early infections reveal how colonies become structured. [Journal Article]
- IJInt J Parasitol 2016 Nov 30
- Recent findings have extended the documentation of complex sociality to the Platyhelminthes, describing the existence of a reproductive division of labour involving a soldier caste among the partheni...
Recent findings have extended the documentation of complex sociality to the Platyhelminthes, describing the existence of a reproductive division of labour involving a soldier caste among the parthenitae of trematode parasites. However, all species examined to date occupy high positions in trematode interspecific dominance hierarchies and belong to two closely related families, the Echinostomatidae and the Philophthalmidae (Superfamily Echinostomatoidea). Further, the two species documented as lacking soldiers also belong to the Echinostomatidae. Here, we examine four species of intermediate dominance, all belonging to the family Heterophyidae (Superfamily Opisthorchioidea): Euhaplorchis californiensis, Phocitremoides ovale, Pygidiopsoides spindalis and Stictodora hancocki, all of which infect the California horn snail, Cerithideopsis californica (=Cerithidea californica). We quantify morphology, distribution and behaviour of rediae from fully developed colonies. We also provide information on colony structure for three developing heterophyid colonies to better understand colony development. We discuss the implications of our findings, particularly with respect to how they suggest alternatives to the conclusions of other researchers concerning the nature of trematode sociality. Our analyses of morphological, distributional and behavioural patterns of developed colonies indicate that these heterophyid trematodes have a non-reproductive caste whose function is defence of the colony from invading trematodes. Hence, a soldier caste occurs for species lower in dominance hierarchies than previously known, and is present in at least two superfamilies of digenean trematodes, suggesting that selection for a soldier caste may be much more common among the Trematoda than previously recognised.
- Plasmodium vivax vaccine research - we've only just begun. [Review]
- IJInt J Parasitol 2016 Nov 27
- Plasmodium vivax parasites cause the majority of malaria cases outside Africa, and are increasingly being acknowledged as a cause of severe disease. The unique attributes of P. vivax biology, particu...
Plasmodium vivax parasites cause the majority of malaria cases outside Africa, and are increasingly being acknowledged as a cause of severe disease. The unique attributes of P. vivax biology, particularly the capacity of the dormant liver stage, the hypnozoite, to maintain blood-stage infections even in the absence of active transmission, make blood-stage vaccines particularly attractive for this species. However, P. vivax vaccine development remains resolutely in first gear, with only a single blood-stage candidate having been evaluated in any depth. Experience with Plasmodium falciparum suggests that a much broader search for new candidates and a deeper understanding of high priority targets will be required to make significant advances. This review discusses some of the particular challenges of P. vivax blood-stage vaccine development, highlighting both recent advances and key remaining barriers to overcome in order to move development forward.
- The s48/45 six-cysteine proteins: mediators of interaction throughout the Plasmodium life cycle. [Review]
- IJInt J Parasitol 2016 Nov 27
- During their life cycle Plasmodium parasites rely upon an arsenal of proteins that establish key interactions with the host or vector, and between the parasite sexual stages, with the purpose of ensu...
During their life cycle Plasmodium parasites rely upon an arsenal of proteins that establish key interactions with the host or vector, and between the parasite sexual stages, with the purpose of ensuring infection, reproduction and proliferation. Among these is a group of secreted or membrane-anchored proteins known as the six-cysteine (6-cys) family. This is a small but important family with only 14 members thus far identified, each stage-specifically expressed during the parasite life cycle. 6-cys proteins often localise at the parasite surface or interface with the host and are conserved in different Plasmodium species. The unifying feature of the family is the s48/45 domain, presumably involved in adhesion and structurally related to Ephrins, the ligands of Eph receptors. The most prominent s48/45 members are currently under functional investigation and are being pursued as vaccine candidates. In this review, we examine what is known about the 6-cys family, their structure and function, and discuss future research directions.
- Novel application of species richness estimators to predict the host range of parasites. [Journal Article]
- IJInt J Parasitol 2016 Nov 27
- Host range is a critical life history trait of parasites, influencing prevalence, virulence and ultimately determining their distributional extent. Current approaches to measure host range are sensit...
Host range is a critical life history trait of parasites, influencing prevalence, virulence and ultimately determining their distributional extent. Current approaches to measure host range are sensitive to sampling effort, the number of known hosts increasing with more records. Here, we develop a novel application of results-based stopping rules to determine how many hosts should be sampled to yield stable estimates of the number of primary hosts within regions, then use species richness estimation to predict host ranges of parasites across their distributional ranges. We selected three mistletoe species (hemiparasitic plants in the Loranthaceae) to evaluate our approach: a strict host specialist (Amyema lucasii, dependent on a single host species), an intermediate species (Amyema quandang, dependent on hosts in one genus) and a generalist (Lysiana exocarpi, dependent on many genera across multiple families), comparing results from geographically-stratified surveys against known host lists derived from herbarium specimens. The results-based stopping rule (stop sampling bioregion once observed host richness exceeds 80% of the host richness predicted using the Abundance-based Coverage Estimator (ACE)) worked well for most bioregions studied, being satisfied after three to six sampling plots (each representing 25 host trees) but was unreliable in those bioregions with high host richness or high proportions of rare hosts. Although generating stable predictions of host range with minimal variation among six estimators trialled, distribution-wide estimates fell well short of the number of hosts known from herbarium records. This mismatch, coupled with the discovery of nine previously unrecorded mistletoe-host combinations, further demonstrates the limited ecological relevance of simple host-parasite lists. By collecting estimates of host range of constrained completeness, our approach maximises sampling efficiency while generating comparable estimates of the number of primary hosts, with broad applicability to many host-parasite systems.
- Cord blood IgG and the risk of severe Plasmodium falciparum malaria in the first year of life. [Journal Article]
- IJInt J Parasitol 2016 Nov 24
- Young infants are less susceptible to severe episodes of malaria but the targets and mechanisms of protection are not clear. Cord blood antibodies may play an important role in mediating protection b...
Young infants are less susceptible to severe episodes of malaria but the targets and mechanisms of protection are not clear. Cord blood antibodies may play an important role in mediating protection but many studies have examined their association with the outcome of infection or non-severe malaria. Here, we investigated whether cord blood IgG to Plasmodium falciparum merozoite antigens and antibody-mediated effector functions were associated with reduced odds of developing severe malaria at different time points during the first year of life. We conducted a case-control study of well-defined severe falciparum malaria nested within a longitudinal birth cohort of Kenyan children. We measured cord blood total IgG levels against five recombinant merozoite antigens and antibody function in the growth inhibition activity and neutrophil antibody-dependent respiratory burst assays. We also assessed the decay of maternal antibodies during the first 6months of life. The mean antibody half-life range was 2.51months (95% confidence interval (CI): 2.19-2.92) to 4.91months (95% CI: 4.47-6.07). The rate of decline of maternal antibodies was inversely proportional to the starting concentration. The functional assay of antibody-dependent respiratory burst activity predicted significantly reduced odds of developing severe malaria during the first 6months of life (Odds ratio (OR) 0.07, 95% CI: 0.007-0.74, P=0.007). Identification of the targets of antibodies mediating antibody-dependent respiratory burst activity could contribute to the development of malaria vaccines that protect against severe episodes of malaria in early infancy.
- The effect of the disulfideisomerase domain containing protein in the defense against polyhexamethylene biguanide of highly tolerant Acanthamoeba at the trophozoite stage. [Journal Article]
- IJInt J Parasitol Drugs Drug Resist 2016 Nov 14; 6(3):251-257
- Acanthamoeba castellanii is a free-living protozoan pathogen capable of causing a blinding keratitis and fatal granulomatous encephalitis. Current treatment generally involves an hourly application o...
Acanthamoeba castellanii is a free-living protozoan pathogen capable of causing a blinding keratitis and fatal granulomatous encephalitis. Current treatment generally involves an hourly application of polyhexamethylene biguanide (PHMB) over a period of several days but this is not entirely effective against all strains/isolates. The tolerance mechanisms of PHMB in Acanthamoeba cells remain unclear. In this study, we found that the mRNA expression level of disulfideisomerase domain containing protein (PDI) increased rapidly in surviving cells of the highly PHMB-tolerant Acanthamoeba castellanii strain, NCKH_D, during PHMB treatment, but not in the ATCC standard strain. After PDI-specific silencing, NCKH_D was found to be more vulnerable to PHMB treatment. The results described above show that PDI is an important gene for PHMB tolerance ability in a highly PHMB-tolerant strain of Acanthamoeba and provide a new insight for more efficient medicine development for Acanthamoeba keratitis.
- Assessment of the national schistosomiasis control program in a typical region along the Yangtze River, China. [Journal Article]
- IJInt J Parasitol 2016 Nov 17
- Schistosomiasis remains a major public health problem in eastern China, particularly along the Yangtze River Basin. The latest national schistosomiasis control program (NSCP) was implemented in 2005 ...
Schistosomiasis remains a major public health problem in eastern China, particularly along the Yangtze River Basin. The latest national schistosomiasis control program (NSCP) was implemented in 2005 with the main goal of reducing the rate of infection to less than 5% by 2008 and 1% by 2015. To assess the progress, we applied a Bayesian spatio-temporal model to describe dynamics of schistosomiasis in Guichi, Anhui Province, China, using annual parasitological and environmental data collected within 41 sample villages for the period 2005-2011. Predictive maps of schistosomiasis showed that the disease prevalence remains constant and low. Results of uncertainty analysis, in the form of probability contour maps (PCMs), indicated that the first goal of "infection rate less than 5% by 2008" was fully achieved in the study area. More longitudinal data for schistosomiasis are needed for the assessment of the second goal of "infection rate less than 1% by 2015". Compared with the traditional way of mapping uncertainty (e.g., variance or mean-square error), our PCMs provide more realistic information for schistosomiasis control.
New Search Next
- Emerging concepts in T follicular helper cell responses to malaria. [Review]
- IJInt J Parasitol 2016 Nov 17
- Antibody responses to malaria and candidate malaria vaccines are short-lived in children, leaving them susceptible to repeated malaria episodes. Because T follicular helper (TFH) cells provide critic...
Antibody responses to malaria and candidate malaria vaccines are short-lived in children, leaving them susceptible to repeated malaria episodes. Because T follicular helper (TFH) cells provide critical help to B cells to generate long-lived antibody responses, they have become the focus of recent studies of Plasmodium-infected mice and humans. The emerging data converge on common themes, namely, that malaria-induced TH1 cytokines are associated with the activation of (i) T-like memory TFH cells with impaired B cell helper function, and (ii) pre-TFH cells that acquire Th1-like features (T-bet expression, IFN-γ production), which impede their differentiation into fully functional TFH cells, thus resulting in germinal center dysfunction and suboptimal antibody responses. Deeper knowledge of TFH cells in malaria could illuminate strategies to improve vaccines through modulating TFH cell responses. This review summarizes emerging concepts in TFH cell responses to malaria.