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1.
PLoS Negl Trop Dis ; 16(8): e0010709, 2022 08.
Article in English | MEDLINE | ID: mdl-35984809

ABSTRACT

BACKGROUND: Infections with Ascaris lumbricoides and Trichuris trichiura remain significant contributors to the global burden of neglected tropical diseases. Infection may in particular affect child development as they are more likely to be infected with T. trichiura and/or A. lumbricoides and to carry higher worm burdens than adults. Whilst the impact of heavy infections are clear, the effects of moderate infection intensities on the growth and development of children remain elusive. Field studies are confounded by a lack of knowledge of infection history, nutritional status, presence of co-infections and levels of exposure to infective eggs. Therefore, animal models are required. Given the physiological similarities between humans and pigs but also between the helminths that infect them; A. suum and T. suis, growing pigs provide an excellent model to investigate the direct effects of Ascaris spp. and Trichuris spp. on weight gain. METHODS AND RESULTS: We employed a trickle infection protocol to mimic natural co-infection to assess the effect of infection intensity, determined by worm count (A. suum) or eggs per gram of faeces (A. suum and T. suis), on weight gain in a large pig population (n = 195) with variable genetic susceptibility. Pig body weights were assessed over 14 weeks. Using a post-hoc statistical approach, we found a negative association between weight gain and T. suis infection. For A. suum, this association was not significant after adjusting for other covariates in a multivariable analysis. Estimates from generalized linear mixed effects models indicated that a 1 kg increase in weight gain was associated with 4.4% (p = 0.00217) decrease in T. suis EPG and a 2.8% (p = 0.02297) or 2.2% (p = 0.0488) decrease in A. suum EPG or burden, respectively. CONCLUSIONS: Overall this study has demonstrated a negative association between STH and weight gain in growing pigs but also that T. suis infection may be more detrimental that A. suum on growth.


Subject(s)
Ascariasis , Swine Diseases , Trichuriasis , Animals , Ascariasis/complications , Ascariasis/epidemiology , Ascariasis/veterinary , Child , Feces/parasitology , Humans , Swine , Swine Diseases/epidemiology , Swine Diseases/parasitology , Trichuriasis/complications , Trichuriasis/epidemiology , Trichuriasis/veterinary , Trichuris/physiology , Weight Gain
2.
Int J Parasitol ; 52(8): 519-524, 2022 07.
Article in English | MEDLINE | ID: mdl-35533731

ABSTRACT

Infections with high doses of intestinal nematodes result in protective immunity based on robust type 2 responses in most mouse lines under laboratory conditions. Here, we report on cellular responses of wild house mice from northern Germany. We detected robust Th1 responses in wild house mice naturally infected with the whipworm Trichuris muris. In contrast, mice infected with pinworms (Syphacia, Aspiculuris) reported type-2 activity by elevated IgG1 levels and eosinophil counts, but also harbored high frequencies of Foxp3+ regulatory T cells, suggesting that natural whip- and pinworm infections induce distinct immunoregulatory as well as effector profiles.


Subject(s)
Enterobiasis , Trichuriasis , Animals , Enterobiasis/veterinary , Immunity , Mice , Th2 Cells , Trichuriasis/veterinary , Trichuris/physiology
3.
Nat Commun ; 13(1): 1725, 2022 04 01.
Article in English | MEDLINE | ID: mdl-35365634

ABSTRACT

Whipworms are large metazoan parasites that inhabit multi-intracellular epithelial tunnels in the large intestine of their hosts, causing chronic disease in humans and other mammals. How first-stage larvae invade host epithelia and establish infection remains unclear. Here we investigate early infection events using both Trichuris muris infections of mice and murine caecaloids, the first in-vitro system for whipworm infection and organoid model for live helminths. We show that larvae degrade mucus layers to access epithelial cells. In early syncytial tunnels, larvae are completely intracellular, woven through multiple live dividing cells. Using single-cell RNA sequencing of infected mouse caecum, we reveal that progression of infection results in cell damage and an expansion of enterocytes expressing of Isg15, potentially instigating the host immune response to the whipworm and tissue repair. Our results unravel intestinal epithelium invasion by whipworms and reveal specific host-parasite interactions that allow the whipworm to establish its multi-intracellular niche.


Subject(s)
Helminths , Trichuriasis , Animals , Intestinal Mucosa , Intestines/parasitology , Mammals , Mice , Trichuris/physiology
4.
Immunity ; 54(1): 151-163.e6, 2021 01 12.
Article in English | MEDLINE | ID: mdl-33220232

ABSTRACT

The gastrointestinal tract is known as the largest endocrine organ that encounters and integrates various immune stimulations and neuronal responses due to constant environmental challenges. Enterochromaffin (EC) cells, which function as chemosensors on the gut epithelium, are known to translate environmental cues into serotonin (5-HT) production, contributing to intestinal physiology. However, how immune signals participate in gut sensation and neuroendocrine response remains unclear. Interleukin-33 (IL-33) acts as an alarmin cytokine by alerting the system of potential environmental stresses. We here demonstrate that IL-33 induced instantaneous peristaltic movement and facilitated Trichuris muris expulsion. We found that IL-33 could be sensed by EC cells, inducing release of 5-HT. IL-33-mediated 5-HT release activated enteric neurons, subsequently promoting gut motility. Mechanistically, IL-33 triggered calcium influx via a non-canonical signaling pathway specifically in EC cells to induce 5-HT secretion. Our data establish an immune-neuroendocrine axis in calibrating rapid 5-HT release for intestinal homeostasis.


Subject(s)
Enterochromaffin Cells/physiology , Interleukin-33/metabolism , Intestines/physiology , Neurons/physiology , Serotonin/metabolism , Trichuriasis/immunology , Trichuris/physiology , Animals , Calcium Signaling , Homeostasis , Interleukin-33/immunology , Mice , Mice, Inbred C57BL , Mice, Knockout , Neuroimmunomodulation , Peristalsis
5.
J Struct Biol ; 212(2): 107611, 2020 11 01.
Article in English | MEDLINE | ID: mdl-32890779

ABSTRACT

Whipworms of the genus Trichuris are nematode parasites that infect mammals and can lead to various intestinal diseases of human and veterinary interest. The most intimate interaction between the parasite and the host intestine occurs through the anterior region of the nematode body, inserted into the intestinal mucosa during infection. One of the most prominent structures of the nematode surface found at the infection site is the bacillary band, a surface domain formed by a number of cells, mostly stichocytes and bacillary glands, whose structure and function are still under debate. Here, we used confocal microscopy, field emission scanning electron microscopy, helium ion microscopy, transmission electron microscopy and FIB-SEM tomography to unveil the functional role of the bacillary gland cell. We analyzed the surface organization as well as the intracellular milieu of the bacillary glands of Trichuris muris in high pressure frozen/freeze-substituted samples. Results showed that the secretory content is preserved in all gland openings, presenting a projected pattern. FIB-SEM analysis showed that the lamellar zone within the bacillary gland chamber is formed by a set of lacunar structures that may exhibit secretory or absorptive functions. In addition, incubation of parasites with the fluid phase endocytosis marker sulforhodamine B showed a time-dependent uptake by the parasite mouth, followed by perfusion through different tissues with ultimate secretion through the bacillary gland. Taken together, the results show that the bacillary gland possess structural characteristics of secretory and absorptive cells and unequivocally demonstrate that the bacillary gland cell functions as a secretory structure.


Subject(s)
Trichuris/physiology , Animals , Endocytosis/physiology , Microscopy, Confocal/methods , Microscopy, Electron, Scanning/methods , Microscopy, Electron, Transmission/methods
6.
J Immunol ; 204(11): 3042-3055, 2020 06 01.
Article in English | MEDLINE | ID: mdl-32284331

ABSTRACT

Fermentable dietary fibers promote the growth of beneficial bacteria, can enhance mucosal barrier integrity, and reduce chronic inflammation. However, effects on intestinal type 2 immune function remain unclear. In this study, we used the murine whipworm Trichuris muris to investigate the effect of the fermentable fiber inulin on host responses to infection regimes that promote distinct Th1 and Th2 responses in C57BL/6 mice. In uninfected mice, dietary inulin stimulated the growth of beneficial bacteria, such as Bifidobacterium (Actinobacteria) and Akkermansia (Verrucomicrobia). Despite this, inulin prevented worm expulsion in normally resistant mice, instead resulting in chronic infection, whereas mice fed an equivalent amount of nonfermentable fiber (cellulose) expelled worms normally. Lack of expulsion in the mice fed inulin was accompanied by a significantly Th1-skewed immune profile characterized by increased T-bet+ T cells and IFN-γ production in mesenteric lymph nodes, increased expression of Ido1 in the cecum, and a complete absence of mast cell and IgE production. Furthermore, the combination of dietary inulin and high-dose T. muris infection caused marked dysbiosis, with expansion of the Firmicutes and Proteobacteria phyla, near elimination of Bacteroidetes, and marked reductions in cecal short-chain fatty acids. Neutralization of IFN-γ during infection abrogated Ido1 expression and was sufficient to restore IgE production and worm expulsion in inulin-fed mice. Our results indicate that, whereas inulin promoted gut health in otherwise healthy mice, during T. muris infection, it exacerbated inflammatory responses and dysbiosis. Thus, the positive effects of fermentable fiber on gut inflammation appear to be context dependent, revealing a novel interaction between diet and infection.


Subject(s)
Dietary Fiber/metabolism , Inflammation/immunology , Inulin/metabolism , Th1 Cells/immunology , Th2 Cells/immunology , Trichuriasis/immunology , Trichuris/physiology , Animals , Disease Progression , Dysbiosis , Fermentation , Gastrointestinal Microbiome , Host-Pathogen Interactions , Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics , Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism , Interferon-gamma/metabolism , Mice , T-Box Domain Proteins/genetics , T-Box Domain Proteins/metabolism
7.
Parasit Vectors ; 13(1): 138, 2020 Mar 16.
Article in English | MEDLINE | ID: mdl-32178706

ABSTRACT

BACKGROUND: Schistosomiasis and infection by soil-transmitted helminths are some of the world's most prevalent neglected tropical diseases. Infection by more than one parasite (co-infection) is common and can contribute to clinical morbidity in children. Geostatistical analyses of parasite infection data are key for developing mass drug administration strategies, yet most methods ignore co-infections when estimating risk. Infection status for multiple parasites can act as a useful proxy for data-poor individual-level or environmental risk factors while avoiding regression dilution bias. Conditional random fields (CRF) is a multivariate graphical network method that opens new doors in parasite risk mapping by (i) predicting co-infections with high accuracy; (ii) isolating associations among parasites; and (iii) quantifying how these associations change across landscapes. METHODS: We built a spatial CRF to estimate infection risks for Ascaris lumbricoides, Trichuris trichiura, hookworms (Ancylostoma duodenale and Necator americanus) and Schistosoma mansoni using data from a national survey of Rwandan schoolchildren. We used an ensemble learning approach to generate spatial predictions by simulating from the CRF's posterior distribution with a multivariate boosted regression tree that captured non-linear relationships between predictors and covariance in infection risks. This CRF ensemble was compared against single parasite gradient boosted machines to assess each model's performance and prediction uncertainty. RESULTS: Parasite co-infections were common, with 19.57% of children infected with at least two parasites. The CRF ensemble achieved higher predictive power than single-parasite models by improving estimates of co-infection prevalence at the individual level and classifying schools into World Health Organization treatment categories with greater accuracy. The CRF uncovered important environmental and demographic predictors of parasite infection probabilities. Yet even after capturing demographic and environmental risk factors, the presences or absences of other parasites were strong predictors of individual-level infection risk. Spatial predictions delineated high-risk regions in need of anthelminthic treatment interventions, including areas with higher than expected co-infection prevalence. CONCLUSIONS: Monitoring studies routinely screen for multiple parasites, yet statistical models generally ignore this multivariate data when assessing risk factors and designing treatment guidelines. Multivariate approaches can be instrumental in the global effort to reduce and eventually eliminate neglected helminth infections in developing countries.


Subject(s)
Coinfection/parasitology , Neglected Diseases/parasitology , Parasitic Diseases/parasitology , Adolescent , Ancylostomatoidea/physiology , Animals , Anthelmintics/therapeutic use , Ascaris lumbricoides/physiology , Child , Coinfection/drug therapy , Coinfection/epidemiology , Feces/parasitology , Female , Humans , Male , Neglected Diseases/drug therapy , Neglected Diseases/epidemiology , Parasitic Diseases/epidemiology , Prevalence , Regression Analysis , Risk Factors , Rwanda , Schistosoma mansoni/physiology , Schistosomiasis mansoni/drug therapy , Trichuris/physiology
8.
Am J Primatol ; 82(2): e23093, 2020 02.
Article in English | MEDLINE | ID: mdl-31930746

ABSTRACT

Ecoimmunological patterns and processes remain understudied in wild primates, in part because of the lack of noninvasive methods to measure immunity. Secretory immunoglobulin A (sIgA) is the most abundant antibody present at mammalian mucosal surfaces and provides an important first line of defense against pathogens. Recent studies show that sIgA can be measured noninvasively in feces and is a good marker of mucosal immunity. Here we validated a commercial ELISA kit to measure fecal IgA in baboons, tested the robustness of its results to variation in collection and storage conditions, and developed a cost-effective in-house ELISA for baboon fecal IgA. Using data from the custom ELISA, we assessed the relationship between fecal IgA concentrations and gastrointestinal parasite burden, and tested how sex, age, and reproductive effort predict fecal IgA in wild baboons. We find that IgA concentrations can be measured in baboon feces using an in-house ELISA and are highly correlated to the values obtained with a commercial kit. Fecal IgA concentrations are stable when extracts are stored for up to 22 months at -20°C. Fecal IgA concentrations were negatively correlated with parasite egg counts (Trichuris trichiura), but not parasite richness. Fecal IgA did not vary between the sexes, but for males, concentrations were higher in adults versus adolescents. Lactating females had significantly lower fecal IgA than pregnant females, but neither pregnant nor lactating female concentrations differed significantly from cycling females. Males who engaged in more mate-guarding exhibited similar IgA concentrations to those who engaged in little mate-guarding. These patterns may reflect the low energetic costs of mucosal immunity, or the complex dependence of IgA excretion on individual condition. Adding a noninvasive measure of mucosal immunity will promote a better understanding of how ecology modulates possible tradeoffs between the immune system and other energetically costly processes in the wild.


Subject(s)
Enzyme-Linked Immunosorbent Assay/veterinary , Immunity, Mucosal , Immunoglobulin A/analysis , Papio anubis/immunology , Papio cynocephalus/immunology , Specimen Handling/veterinary , Age Factors , Animals , Animals, Wild/immunology , Animals, Zoo/immunology , Enzyme-Linked Immunosorbent Assay/methods , Female , Kenya , Male , Monkey Diseases/immunology , Monkey Diseases/parasitology , North Carolina , Reproduction , Sex Factors , Specimen Handling/methods , Trichuriasis/immunology , Trichuriasis/parasitology , Trichuriasis/veterinary , Trichuris/physiology
9.
Acta Trop ; 204: 105347, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31954684

ABSTRACT

The soil transmitted whipworm, Trichuris trichiura affects about half a billion people globally. Diagnosis is based on identification of characteristic lemon-shaped eggs in stool samples. Occasionally large Trichuris eggs have been reported and have been ascribed to variation within T. trichiura or zoonotic infection with T. vulpis from dogs. We observed that the egg size profile changed markedly after anthelmintic treatment, and remained so, in a human individual self-infected with T. trichiura. The large eggs were detected with two standard diagnostic methods, Kato-Katz thick smear and salt-flotation (McMaster) method. It is therefore important to bear in mind that the morphology of parasite eggs may vary, e.g. in response to previous drug treatment. Large Trichuris eggs in human stool samples should not be diagnosed as T. vulpis infection without confirmation by other means.


Subject(s)
Anthelmintics/therapeutic use , Mebendazole/therapeutic use , Trichuriasis/drug therapy , Trichuris/physiology , Adult , Animals , Anthelmintics/pharmacology , Feces/parasitology , Humans , Male , Mebendazole/pharmacology , Parasite Egg Count , Trichuris/drug effects , Zoonoses/drug therapy
10.
World J Biol Psychiatry ; 21(4): 291-299, 2020 04.
Article in English | MEDLINE | ID: mdl-30230399

ABSTRACT

Objectives: Inflammatory mechanisms are implicated in the aetiology of autism spectrum disorder (ASD), and use of the immunomodulator Trichuris suis Ova (TSO) is a novel treatment approach. This pilot study determined the effect sizes for TSO versus placebo on repetitive behaviours, irritability and global functioning in adults with ASD.Methods: A 28-week double-blind, randomised two-period crossover study of TSO versus placebo in ten ASD adults, aged 17-35, was completed, with a 4-week washout between each 12-week period at Montefiore Medical Center, Albert Einstein College of Medicine. Subjects with ASD, history of seasonal, medication or food allergies, Y-BOCS ≥6 and IQ ≥70 received 2,500 TSO ova or matching placebo every 2 weeks of each 12-week period.Results: Large effect sizes for improvement in repetitive behaviours (d = 1.0), restricted interests (d = 0.82), rigidity (d = 0.79) and irritability (d = 0.78) were observed after 12 weeks of treatment. No changes were observed in the social-communication domain. Differences between treatment groups did not reach statistical significance. TSO had only minimal, non-serious side effects.Conclusions: This proof-of-concept study demonstrates the feasibility of TSO for the treatment of ASD, including a favourable safety profile, and moderate to large effect sizes for reducing repetitive behaviours and irritability.Clinicaltrials.gov: NCT01040221.


Subject(s)
Autism Spectrum Disorder , Behavior , Irritable Mood , Therapy with Helminths , Trichuris , Adolescent , Adult , Animals , Autism Spectrum Disorder/complications , Autism Spectrum Disorder/parasitology , Autism Spectrum Disorder/therapy , Behavior/physiology , Cross-Over Studies , Double-Blind Method , Feasibility Studies , Humans , Hypersensitivity/complications , Hypersensitivity/therapy , Irritable Mood/physiology , Ovum , Pilot Projects , Therapy with Helminths/standards , Trichuriasis , Trichuris/physiology , Young Adult
11.
Infect Dis Poverty ; 8(1): 82, 2019 Oct 02.
Article in English | MEDLINE | ID: mdl-31575378

ABSTRACT

BACKGROUND: The goal of soil-transmitted helminthiases (STH) control programmes is to eliminate STH-associated morbidity in the target population by reducing the prevalence of moderate- and heavy-intensity infections and the overall STH infection prevalence mainly through preventive chemotherapy (PC) with either albendazole or mebendazole. Endemic countries should measure the success of their control programmes through regular epidemiological assessments. We evaluated changes in STH prevalence in countries that conducted effective PC coverage for STH to guide changes in the frequency of PC rounds and the number of tablets needed. METHODS: We selected countries from World Health Organization (WHO)'s Preventive Chemotherapy and Transmission control (PCT) databank that conducted ≥5 years of PC with effective coverage for school-age children (SAC) and extracted STH baseline and impact assessment data using the WHO Epidemiological Data Reporting Form, Ministry of Health reports and/or peer-reviewed publications. We used pooled and weighted means to plot the prevalence of infection with any STH and with each STH species at baseline and after ≥5 years of PC with effective coverage. Finally, using the WHO STH decision tree, we estimated the reduction in the number of tablets needed. RESULTS: Fifteen countries in four WHO regions conducted annual or semi-annual rounds of PC for STH for 5 years or more and collected data before and after interventions. At baseline, the pooled prevalence was 48.9% (33.1-64.7%) for any STH, 23.2% (13.7-32.7%) for Ascaris lumbricoides, 21.01% (9.7-32.3%) for Trichuris trichiura and 18.2% (10.9-25.5%) for hookworm infections, while after ≥5 years of PC for STH, the prevalence was 14.3% (7.3-21.3%) for any STH, 6.9% (1.3-12.5%) for A. lumbricoides, 5.3% (1.06-9.6%) for T. trichiura and 8.1% (4.0-12.2%) for hookworm infections. CONCLUSIONS: Countries endemic for STH have made tremendous progress in reducing STH-associated morbidity, but very few countries have data to demonstrate that progress. In this study, the data show that nine countries should adapt their PC strategies and the frequency of PC rounds to yield a 36% reduction in drug needs. The study also highlights the importance of impact assessment surveys to adapt control strategies according to STH prevalence.


Subject(s)
Albendazole/therapeutic use , Anthelmintics/therapeutic use , Chemoprevention/statistics & numerical data , Helminthiasis/prevention & control , Mebendazole/therapeutic use , Albendazole/supply & distribution , Animals , Anthelmintics/supply & distribution , Ascariasis/epidemiology , Ascariasis/parasitology , Ascariasis/prevention & control , Ascaris lumbricoides/physiology , Helminthiasis/epidemiology , Helminthiasis/parasitology , Hookworm Infections/epidemiology , Hookworm Infections/parasitology , Hookworm Infections/prevention & control , Humans , Mebendazole/supply & distribution , Prevalence , Soil/parasitology , Trichuriasis/epidemiology , Trichuriasis/parasitology , Trichuriasis/prevention & control , Trichuris/physiology
12.
J Exp Med ; 216(6): 1268-1279, 2019 06 03.
Article in English | MEDLINE | ID: mdl-30975892

ABSTRACT

Type 2 inflammation drives the clearance of gastrointestinal helminth parasites, which infect over two billion people worldwide. Basophils are innate immune cells that support host-protective type 2 inflammation during murine infection with the helminth Trichuris muris However, the mechanisms required for basophil function and gene expression regulation in this context remain unclear. We show that during T. muris infection, basophils localized to the intestine and up-regulated Notch receptor expression, rendering them sensitive to Notch signals that rapidly regulate gene expression programs. In vitro, Notch inhibition limited basophil cytokine production in response to cytokine stimulation. Basophil-intrinsic Notch signaling was required for T. muris-elicited changes in genome-wide basophil transcriptional programs. Mice lacking basophil-intrinsic functional Notch signaling had impaired worm clearance, decreased intestinal type 2 inflammation, altered basophil localization in the intestine, and decreased CD4+ T helper 2 cell responses following infection. These findings demonstrate that Notch is required for basophil gene expression and effector function associated with helminth expulsion during type 2 inflammation.


Subject(s)
Basophils/immunology , Inflammation/pathology , Receptors, Notch/metabolism , Signal Transduction , Animals , Cecum/parasitology , Female , Gene Expression Regulation , Inflammation/complications , Interleukins/metabolism , Male , Mice, Inbred C57BL , Trichuris/physiology , Up-Regulation
13.
J Helminthol ; 93(5): 552-558, 2019 Sep.
Article in English | MEDLINE | ID: mdl-30001752

ABSTRACT

The yellow-necked mouse, Apodemus flavicollis, can be considered as a model for genetic polymorphism produced by the frequent presence of supernumerary or B chromosomes (Bs). Host genetic background is rarely taken into account in studies of parasite sex ratio. The main aim of this study was to investigate the range of infrapopulation sex ratios for nematode parasites of the yellow-necked mouse and to determine which factors most influence variation in parasite sex ratios. Six nematode species found in the collected yellow-necked mice were analysed. We confirmed the predominant pattern of female-biased sex ratios in vertebrate parasite infrapopulations. The presence of B chromosomes in host genomes played an important role in infrapopulations of Heligmosomoides polygyrus, Syphacia stroma and Trichuris muris, as hosts with B chromosomes carried a higher proportion of males. The relative increase of males in infrapopulations could result from a shift in parasite life history strategy, induced by adaptation to the specific host genotypes (Bs present). In a meta-analysis with previously published data, the sex determination system was demonstrated to play a significant role in nematode sex ratio variation, as well as specific life history patterns, such as the place of egg hatching.


Subject(s)
Chromosomes , Host-Parasite Interactions/genetics , Murinae/genetics , Nematoda/physiology , Sex Ratio , Animals , Female , Genome , Male , Murinae/parasitology , Nematospiroides dubius/physiology , Serbia , Sex Determination Processes , Trichuris/physiology
14.
Mucosal Immunol ; 12(2): 352-362, 2019 03.
Article in English | MEDLINE | ID: mdl-30401814

ABSTRACT

The ability of helminths to manipulate the immune system of their hosts to ensure their own survival is often credited with affecting responses to other pathogens. We undertook co-infection experiments in mice to determine how infection with the intestinal helminth Heligmosomoides polygyrus affected the parasitological, immunological and physiological outcomes of a primary infection with a distinct species of helminth; the lung migratory parasite Nippostrongylus brasiliensis. We found that migrating N. brasiliensis larvae were killed in the lungs of H. polygyrus-infected mice by a process involving IL-33-activated CD4+ T cells that released IL-5 and recruited activated eosinophils. The lung pathology normally associated with N. brasiliensis larval migration was also reduced. Importantly, lung immunity remained intact in mice cleared of prior H. polygyrus infection and also occurred during infection with another entirely enteric helminth, Trichuris muris. This study identifies a cross-mucosal immune mechanism by which intestinal helminths may protect their hosts against co-infection by a different parasite at a distal site, via circulation of activated CD4+ T cells that can be triggered to release effector cytokines and mount inflammatory responses by tissue damage-associated alarmins, such as IL-33.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , Coinfection , Eosinophils/immunology , Interleukin-5/metabolism , Lung/immunology , Nematospiroides dubius/physiology , Nippostrongylus/physiology , Strongylida Infections/immunology , Trichuriasis/immunology , Trichuris/physiology , Animals , Antigens, Helminth/immunology , Cell Movement , Cells, Cultured , Cytotoxicity, Immunologic , Female , Host-Parasite Interactions , Immunity , Interleukin-33/metabolism , Lung/parasitology , Mice , Mice, Inbred C57BL , Mice, Knockout
15.
Proc Biol Sci ; 285(1888)2018 10 03.
Article in English | MEDLINE | ID: mdl-30282648

ABSTRACT

Throughout history, humans have been afflicted by parasitic worms, and eggs are readily detected in archaeological deposits. This study integrated parasitological and ancient DNA methods with a large sample set dating between Neolithic and Early Modern periods to explore the utility of molecular archaeoparasitology as a new approach to study the past. Molecular analyses provided unequivocal species-level parasite identification and revealed location-specific epidemiological signatures. Faecal-oral transmitted nematodes (Ascaris lumbricoides and Trichuris trichiura) were ubiquitous across time and space. By contrast, high numbers of food-associated cestodes (Diphyllobothrium latum and Taenia saginata) were restricted to medieval Lübeck. The presence of these cestodes and changes in their prevalence at approximately 1300 CE indicate substantial alterations in diet or parasite availability. Trichuris trichiura ITS-1 sequences grouped into two clades; one ubiquitous and one restricted to medieval Lübeck and Bristol. The high sequence diversity of T.tITS-1 detected in Lübeck is consistent with its importance as a Hanseatic trading centre. Collectively, these results introduce molecular archaeoparasitology as an artefact-independent source of historical evidence.


Subject(s)
Cultural Evolution , Feces/parasitology , Helminths/physiology , Trichuriasis/history , Animals , Archaeology , Cities/epidemiology , DNA, Ancient/analysis , Genetic Variation , Germany/epidemiology , Helminths/classification , History, 15th Century , History, 16th Century , History, 17th Century , History, Ancient , History, Medieval , Humans , Parasite Egg Count , Parasitology , Trichuriasis/epidemiology , Trichuriasis/parasitology , Trichuris/genetics , Trichuris/physiology
16.
Ann Agric Environ Med ; 25(3): 460-463, 2018 Sep 25.
Article in English | MEDLINE | ID: mdl-30260190

ABSTRACT

INTRODUCTION: While using recreational areas, people take with them accompanying animals (dogs, cats). These animals are the main source and reservoir of dangerous zoonoses, including parasitoses caused by genera of nematodes, also called roundworms, Toxocara spp., Trichuris spp. and Ancylostoma spp. Attention should also be paid to the possibility of contamination of recreational areas with the eggs of intestinal parasites by wild animals (e.g. red fox). MATERIAL AND METHODS: Sand was collected on beaches and leisure terrains located in recreational areas in Zwierzyniec, Rudka reservoir on the river Wieprz, 'Echo' reservoir, accessible to tourists to the Roztocze National Park, and the 'Florianiecki' reservoir, chich is inaccessible to tourists due to its location in the depths of the National Park. Material for the research was also collected from the 'Zemborzycki reservoir in Lublin, A total of 300 sand samples were collected. The samples, approximately 500 g each, were collected into plastic bags from the superficial layer of sand, at a depth up to 3 cm. For egg detection, flotation with the Wasylikowa metod and the modified Quinn method were used. In the Quinn metod, the flotation solution is NaCl saturated solution, in the Wasylikowa method, 5% solution of NaOH is used. RESULTS: The most contaminated grounds were areas by the water 'Zemborzycki' reservoir in Lublin. The eggs of intestinal parasites were isolated from 13 out of 24 samples examined. In sand collected from the beach by the 'Echo', 'Florianiecki' and 'Rudka' water resevoirs in Zwierzyniec, no eggs of intestinal parasites were detected. CONCLUSIONS: Such a dissemination of results may indicate a connection between the degree of occurrence of geohelmint eggs and the intensity of human movement, together with accompanying animals, in places that can be used for recreation.


Subject(s)
Ancylostoma/isolation & purification , Ovum/chemistry , Soil/parasitology , Toxocara/isolation & purification , Trichuris/isolation & purification , Ancylostoma/physiology , Animals , Environmental Monitoring , Feces/parasitology , Humans , Parasite Egg Count , Poland , Recreation , Toxocara/physiology , Trichuris/physiology
17.
Front Immunol ; 9: 850, 2018.
Article in English | MEDLINE | ID: mdl-29760697

ABSTRACT

Gastrointestinal (GI) parasites, hookworms in particular, have evolved to cause minimal harm to their hosts, allowing them to establish chronic infections. This is mediated by creating an immunoregulatory environment. Indeed, hookworms are such potent suppressors of inflammation that they have been used in clinical trials to treat inflammatory bowel diseases (IBD) and celiac disease. Since the recent description of helminths (worms) secreting extracellular vesicles (EVs), exosome-like EVs from different helminths have been characterized and their salient roles in parasite-host interactions have been highlighted. Here, we analyze EVs from the rodent parasite Nippostrongylus brasiliensis, which has been used as a model for human hookworm infection. N. brasiliensis EVs (Nb-EVs) are actively internalized by mouse gut organoids, indicating a role in driving parasitism. We used proteomics and RNA-Seq to profile the molecular composition of Nb-EVs. We identified 81 proteins, including proteins frequently present in exosomes (like tetraspanin, enolase, 14-3-3 protein, and heat shock proteins), and 27 sperm-coating protein-like extracellular proteins. RNA-Seq analysis revealed 52 miRNA species, many of which putatively map to mouse genes involved in regulation of inflammation. To determine whether GI nematode EVs had immunomodulatory properties, we assessed their potential to suppress GI inflammation in a mouse model of inducible chemical colitis. EVs from N. brasiliensis but not those from the whipworm Trichuris muris or control vesicles from grapes protected against colitic inflammation in the gut of mice that received a single intraperitoneal injection of EVs. Key cytokines associated with colitic pathology (IL-6, IL-1ß, IFNγ, and IL-17a) were significantly suppressed in colon tissues from EV-treated mice. By contrast, high levels of the anti-inflammatory cytokine IL-10 were detected in Nb-EV-treated mice. Proteins and miRNAs contained within helminth EVs hold great potential application in development of drugs to treat helminth infections as well as chronic non-infectious diseases resulting from a dysregulated immune system, such as IBD.


Subject(s)
Colitis/prevention & control , Exosomes/immunology , Extracellular Vesicles/physiology , Hookworm Infections/immunology , Host-Parasite Interactions , Nippostrongylus/physiology , Animals , Colitis/chemically induced , Cytokines/immunology , Disease Models, Animal , Female , Immunomodulation , Inflammation/genetics , Interleukin-10/immunology , Macrophages/immunology , Mice , Mice, Inbred C57BL , MicroRNAs/genetics , Proteomics , Sequence Analysis, RNA , Trichuris/physiology
18.
PLoS Negl Trop Dis ; 12(5): e0006483, 2018 05.
Article in English | MEDLINE | ID: mdl-29746467

ABSTRACT

Multi-species interactions can often have non-intuitive consequences. However, the study of parasite interactions has rarely gone beyond the effects of pairwise combinations of species, and the outcomes of multi-parasite interactions are poorly understood. We investigated the effects of co-infection by four gastrointestinal helminth species on the development of cerebral malaria among Plasmodium falciparum-infected patients. We characterized associations among the helminth parasite infra-community, and then tested for independent (direct) and co-infection dependent (indirect) effects of helminths on cerebral malaria risk. We found that infection by Ascaris lumbricoides and Trichuris trichiura were both associated with direct reductions in cerebral malaria risk. However, the benefit of T. trichiura infection was halved in the presence of hookworm, revealing a strong indirect effect. Our study suggests that the outcome of interactions between two parasite species can be significantly modified by a third, emphasizing the critical role that parasite community interactions play in shaping infection outcomes.


Subject(s)
Ascariasis/parasitology , Ascaris lumbricoides/physiology , Coinfection/parasitology , Malaria, Cerebral/parasitology , Plasmodium falciparum/physiology , Trichuriasis/parasitology , Trichuris/physiology , Adult , Animals , Female , Humans , Male , Young Adult
19.
Sci Adv ; 4(3): eaap7399, 2018 03.
Article in English | MEDLINE | ID: mdl-29546242

ABSTRACT

Intestinal dwelling parasites have evolved closely with the complex intestinal microbiota of their host, but the significance of the host microbiota for metazoan pathogens and the role of their own intestinal microbiota are still not fully known. We have found that the parasitic nematode Trichuris muris acquired a distinct intestinal microbiota from its host, which was required for nematode fitness. Infection of germ-free mice and mice monocolonized with Bacteroides thetaiotaomicron demonstrated that successful T. muris infections require a host microbiota. Following infection, T. muris-induced alterations in the host intestinal microbiota inhibited subsequent rounds of infection, controlling parasite numbers within the host intestine. This dual strategy could promote the long-term survival of the parasite within the intestinal niche necessary for successful chronic nematode infection.


Subject(s)
Host-Parasite Interactions , Microbiota , Parasites/microbiology , Trichuriasis/microbiology , Trichuris/physiology , Adaptive Immunity/drug effects , Animals , Anti-Bacterial Agents/pharmacology , Host-Parasite Interactions/drug effects , Host-Parasite Interactions/immunology , Intestines/microbiology , Intestines/parasitology , Mice, Inbred C57BL , Microbiota/drug effects , Parasites/drug effects , Parasites/immunology , Trichuriasis/immunology , Trichuris/drug effects
20.
J Infect Public Health ; 11(2): 197-202, 2018.
Article in English | MEDLINE | ID: mdl-28797540

ABSTRACT

Morocco is a country known for its vulnerability of water resources because of its arid and semi-arid climate. Thus, recycled wastewater has been suggested for agricultural activities, but contamination of these wastewaters is a major concern. The current study aims to determine the occurrence of helminth eggs in urban wastewater and to evaluate the removal of these pathogens by two sewage treatment systems: activated sludge and natural lagoons. The samples of wastewater and sludge were collected from two wastewater treatment plants (WWTP) located in Marrakech and Chichaoua, Morocco. Parasitological identification, according to the Bailenger technique, showed the presence of Nematodes and Cestodes, which are pathogenic to humans and animals and are responsible for helminthiasis. The wastewater and sewage sludge samples from Marrakech carried Ascaris lumbricoïdes, Ancylostoma duodenale, Trichuris trichiura, Capillaria spp., Taenia spp. and Hymenolepis spp., while the samples from Chichaoua carried Ascaris lumbricoïdes, Ancylostoma duodenale, Trichuris trichiura and Capillaria spp. The overall removal efficiency of eggs in the treatment plants ranged from 100% in the WWTP of Marrakech using activate sludge to 94.97% in the WWTP of Chichaoua using natural lagoons. These results were discussed according to health risk and the cost-effectiveness of both wastewater treatment techniques.


Subject(s)
Helminthiasis/prevention & control , Helminths/isolation & purification , Parasite Egg Count/methods , Sewage/parasitology , Water Purification/methods , Agriculture , Animals , Helminthiasis/epidemiology , Helminths/classification , Helminths/physiology , Lakes/parasitology , Morocco/epidemiology , Parasite Egg Count/instrumentation , Taenia/isolation & purification , Trichuris/isolation & purification , Trichuris/physiology , Waste Disposal, Fluid
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