Rodent Nematode Research Articles

REDESCRIPTION OF HASSALSTRONGYLUS ADUNCUS CHANDLER, 1932 (NEMATODA: HELIGMONELLIDAE), WITH THE DESCRIPTION OF A NEW SPECIES OF THE GENUS AND THEIR PHYLOGENETIC POSITION WITH OTHER HELIGMOSOMOIDEA TRAVASSOS, 1914.

Hassalstrongylus Durette-Desset, 1971 (Nematoda: Heligmonellidae), includes 19 species that are distributed from the southwestern United States to central-western Argentina. Hassalstrongylus aduncus is a parasitic nematode of rodents from the subfamilies Arvicolinae, Murinae, and Sigmodontinae, and has been recorded from southern Virginia and Oklahoma to Costa Rica. This species was described by Chandler in 1932; the morphology of the synlophe was not included. Subsequently, in 1972, Durette-Desset described only the synlophe of the middle region of the body in both sexes. Despite its wide geographical distribution, to date, there has been no redescription that includes information complementary to the morphology of the synlophe, such as a study of the body surface or a molecular phylogenetic analysis. We reevaluated the morphology of some specimens that were presumably similar to H. aduncus parasite of Sigmodon sp. from Jalisco, Mexico, and it was determined that these corresponded to an undescribed species of the genus. Herein, we present a redescription of H. aduncus parasite of Sigmodon toltecus from Hidalgo, Mexico, with morphological traits such as the excretory pore, deirids, and ovijector, and provide a description of the synlophe in the anterior and posterior regions of both sexes and include scanning electron microscopy images. Hassalstrongylus geolayarum n. sp. is differentiated from H. aduncus by the number of ridges in the middle region of the body (23 vs. 21), as well as proportions between some traits of males and females such as total length/spicule length, total length/gubernaculum length, total length/length of the esophagus and total length/distance of the vulva and the size of the eggs (42 vs. 58 μm). Phylogenetic analysis is based on partial sequences of the nuclear ribosomal internal transcribed spacer region (ITS1 + 5.8S + ITS2) of the rDNA, using the maximum-parsimony, maximum-likelihood, and Bayesian inference methods revealed the close relationship of H. aduncus + H. geolayarum n. sp. within the Heligmosomoidea and confirmed the placement of the Hassalstrongylus monophyletic clade well-supported within Heligmonellidae. The new species presented a genetic divergence of 3.4-3.8% relative to H. aduncus. This is the first species of the genus described in Mexico. Presumably, there are more species not yet described throughout the geographic range of H. aduncus. A taxonomic review and molecular phylogenetic analysis are required in which more species and genes are analyzed in Heligmosomoidea to confirm the status of the nonmonophyletic groups recovered here.

Helminth infection driven gastrointestinal hypermotility is independent of eosinophils and mediated by alterations in smooth muscle instead of enteric neurons.

Intestinal helminth infection triggers a type 2 immune response that promotes a 'weep-and sweep' response characterised by increased mucus secretion and intestinal hypermotility, which function to dislodge the worm from its intestinal habitat. Recent studies have discovered that several other pathogens cause intestinal dysmotility through major alterations to the immune and enteric nervous systems (ENS), and their interactions, within the gastrointestinal tract. However, the involvement of these systems has not been investigated for helminth infections. Eosinophils represent a key cell type recruited by the type 2 immune response and alter intestinal motility under steady-state conditions. Our study aimed to investigate whether altered intestinal motility driven by the murine hookworm, Nippostrongylus brasiliensis, infection involves eosinophils and how the ENS and smooth muscles of the gut are impacted. Eosinophil deficiency did not influence helminth-induced intestinal hypermotility and hypermotility did not involve gross structural or functional changes to the ENS. Hypermotility was instead associated with a dramatic increase in smooth muscle thickness and contractility, an observation that extended to another rodent nematode, Heligmosomoides polygyrus. In summary our data indicate that, in contrast to other pathogens, helminth-induced intestinal hypermotility is driven by largely by myogenic, rather than neurogenic, alterations with such changes occurring independently of eosinophils. (<300 words).

The IL-17A-neutrophil axis promotes epithelial cell IL-33 production during nematode lung migration

The early migratory phase of pulmonary helminth infections is characterized by tissue injury leading to the release of the alarmin interleukin (IL)-33 and subsequent induction of type 2 immune responses. We recently described a role for IL-17A, through suppression of interferon (IFN)-γ, as an important inducer of type 2 responses during infection with the lung-migrating rodent nematode Nippostrongylus brasiliensis. Here, we aimed to investigate the interaction between IL-17A and IL-33 during the early lung migratory stages of N. brasiliensis infection. In this brief report, we demonstrate that deficiency of IL-17A leads to impaired IL-33 expression and secretion early in infection, independent of IL-17A suppression of IFN-γ. Neutrophil-depletion experiments, which dramatically reduce lung injury, revealed that neutrophils are primarily responsible for the IL-17A-dependent release of IL-33 into the airways. Taken together, our results reveal an IL-17A-neutrophil-axis that can drive IL-33 during helminth infection, highlighting an additional pathway by which IL-17A regulates pulmonary type 2 immunity.

Novel High-Throughput Fluorescence-Based Assay for the Identification of Nematocidal Compounds That Target the Blood-Feeding Pathway.

Hookworm infections cause a neglected tropical disease (NTD) affecting ~740 million people worldwide, principally those living in disadvantaged communities. Infections can cause high morbidity due to their impact on nutrient uptake and their need to feed on host blood, resulting in a loss of iron and protein, which can lead to severe anaemia and impaired cognitive development in children. Currently, only one drug, albendazole is efficient to treat hookworm infection and the scientific community fears the rise of resistant strains. As part of on-going efforts to control hookworm infections and its associated morbidities, new drugs are urgently needed. We focused on targeting the blood-feeding pathway, which is essential to the parasite survival and reproduction, using the laboratory hookworm model Nippostrongylus brasiliensis (a nematode of rodents with a similar life cycle to hookworms). We established an in vitro-drug screening assay based on a fluorescent-based measurement of parasite viability during blood-feeding to identify novel therapeutic targets. A first screen of a library of 2654 natural compounds identified four that caused decreased worm viability in a blood-feeding-dependent manner. This new screening assay has significant potential to accelerate the discovery of new drugs against hookworms.

Capillaria hepatica (syn. Calodium hepaticum) as a Cause of Asymptomatic Liver Mass

Capillaria hepatica (syn. Calodium hepaticum) is a parasitic nematode of rodents, rarely infecting humans. An asymptomatic Israeli adult male with extensive travel history was diagnosed with a liver mass on routine post-thymectomy follow-up. Imaging and computer tomography (CT) guided biopsy were inconclusive. Surgical excision revealed an eosinophilic granuloma with fragments of a nematode suspected to be C. hepatica. Molecular methods verified the diagnosis, and the patient was treated empirically. This is the first case of hepatic capillariasis described in Israel, and the first to be diagnosed using molecular methods.

Anthelmintic Effect of Date Palm Fruit: A Systematic Review

Soil-transmitted helminth infections constitute a global affliction affecting people and livestock, resulting in a significant disease burden and economic losses in endemic regions. However, control has not been entirely successful and the problem is compounded by the development of resistance to available chemotherapy. Novel alternative compounds are urgently needed, encouraging the screening of largely plant-based sources for anthelmintic effects. Date palm fruit (Phoenix dactylifera) is a popular and nutritious food much coveted for its nutraceutical effect. There are convincing reports documenting the antibacterial, antiviral and antifungal effects of date palm fruit but evidence for any potential anthelmintic effect remains unclear. Here we conducted a systematic review of the published information through an electronic search using six scientific databases; SCOPUS, MEDLINE COMPLETE, OVID, EMBASE, WEB OF SCIENCE and CINAHL COMPLETE. Out of 58 studies that were initially identified only 2 manuscripts fitted our inclusion criteria. The first article reported on the anthelmintic effect of date palm fruit against the rodent nematodes Trichuris muris and Angiostrongylus cantonensis in vitro and in vivo while the second article was based only on in vivo assessment (with coconut) of the effect on the rodent cestode Hymenolepis microstoma. Our review revealed limited anecdotal reports of the anthelmintic effect of date palm fruit against parasitic helminths, however, the majority of reports were inconclusive due to mixed results, limited focus on date palm fruit and lack of any statistical analyses. Rigorous, systematic and fully controlled studies focusing on date palm fruit are needed to validate the anecdotal evidence.

A novel blood-feeding detoxification pathway in Nippostrongylus brasiliensis L3 reveals a potential checkpoint for arresting hookworm development.

As part of on-going efforts to control hookworm infection, the “human hookworm vaccine initiative” has recognised blood feeding as a feasible therapeutic target for inducing immunity against hookworm infection. To this end, molecular approaches have been used to identify candidate targets, such as Necator americanus (Na) haemoglobinase aspartic protease-1 (APR-1), with immunogenicity profiled in canine and hamster models. We sought to accelerate the immune analysis of these identified therapeutic targets by developing an appropriate mouse model. Here we demonstrate that Nippostrongylus brasiliensis (Nb), a phylogenetically distant strongylid nematode of rodents, begins blood feeding early in its development and that immunisation with Na-APR-1 can block its growth and completion of its life cycle. Furthermore, we identify a new haem detoxification pathway in Nb required for blood feeding that can be blocked by drugs of the quinolone family, reducing both infection burden and the associated anaemia in rodents. Collectively, our findings show that haem metabolism has potential as a checkpoint for interrupting hookworm development in early stages of the hookworm life cycle and that the Nippostrongylus brasiliensis rodent model is relevant for identifying novel therapeutic targets against human hookworm.

Nematodes of rodents of Armenia

This review summarizes known data on the species composition of nematodes in 24 species of rodents inhabiting the territory of Armenia (South of Lesser Caucasus). The studied rodents include members of some cosmopolitan species (Mus musculus, Rattus norvegicus, Rattus rattus), as well as endemic and narrow-areal species (Meriones vinogradovi, Spermophilus xanthoprymnus, Microtus schidlovskii, Mesocricetus brandti, Sciurus anomalus). The taxonomical identity of the nematode species reported by previous authors is discussed with regard to present knowledge about helminth fauna of rodents. Our review concludes that 34 nematode species are present in rodents in Armenia, five of which are identified for the first time in rodents from the territory of Armenia, and three of which (Trichinella spiralis, Trichostrongylus colubriformis, Trichostrongylus skrjabini) are able to parasitize humans.

Venestatin, a Ca++-binding protein from the parasitic nematode Strongyloides venezuelensis, is involved in the larval migration process

The secretory EF-hand Ca++-binding proteins act as calcium signaling molecules for control of cell functions, but those proteins from parasitic helminths are poorly understood. Here, we have identified and characterized an EF-hand Ca++-binding protein from the rodent nematode, Strongyloides venezuelensis, termed ‘venestatin’, which is highly conserved in Strongyloides spp. Canonical two EF-hand domains and a signal peptide are present in venestatin. A gel mobility shift assay and Ruthenium red staining indicated that the recombinant venestatin possesses binding ability with Ca++ ions. Endogenous venestatin was seemingly localized in the hypodermis and gut of the worms and was found in the excretory-secretory products. Quantitative reverse transcription-PCR data showed that venestatin-specific transcript was upregulated in the parasitic stages of S. venezuelensis, and the upregulation occurred promptly after larval invasion through the host’s skin, but not in the case of in vitro incubation. Immunization of mice with recombinant venestatin caused a 55% reduction in larval migration to the lungs, and lung hemorrhaging was mild compared with non-immunized groups, suggesting that anti-venestatin sera may interfere with larval migration from skin to lung. Our results suggest that venestatin is secreted from the hypodermis and gut of S. venezuelensis, and has pivotal roles in larval migration.

Potential immunological markers for diagnosis of human strongyloidiasis using heterologous antigens.

Strongyloides venezuelensis is a parasitic nematode of rodents that is frequently used to obtain heterologous antigens for immunological diagnosis of human strongyloidiasis. The aim of this study was to identify antigens from filariform larvae of S. venezuelensis for immunodiagnosis of human strongyloidiasis. Soluble and membrane fractions from filariform larvae of S. venezuelensis were obtained in phosphate saline (SS and SM) and in Tris-HCl buffer (TS and TM), and were analysed by Western blotting. Different antigenic components were recognized by IgG antibodies from the sera of strongyloidiasis patients. Highest recognition was observed for a 30-40 kDa mass range present in all antigenic fractions. The band encompassing this mass range was then excised and subjected to mass spectrometry for protein identification. Immunoreactive proteins identified in the soluble fractions corresponded to metabolic enzymes, whereas cytoskeletal proteins and galectins were more abundant in the membrane fractions. These results represent the first approach towards identification of S. venezuelensis antigens for use in immunodiagnostic assays for human strongyloidiasis.

Microglia activation: one of the checkpoints in the CNS inflammation caused by Angiostrongylus cantonensis infection in rodent model.

Angiostrongylus cantonensis (A. cantonensis) is a rodent nematode. Adult worms of A. cantonensis live in the pulmonary arteries of rats; humans are non-permissive hosts like the mice. The larva cannot develop into an adult worm and only causes serious eosinophilic meningitis or meningo-encephalitis if humans or mice eat food containing larva of A. cantonensis in the third stage. The differing consequences largely depend on differing immune responses of hosts to parasite during A. cantonensis invasion and development. To further understand the reasons why mice and rats attain different outcomes in A. cantonensis infection, we used the HE staining to observe the pathological changes of infected mice and rats. In addition, we measured mRNA levels of some cytokines (IL-5, IL-6, IL-13, Eotaxin, IL-4, IL-10, TGF-β, IFN-γ, IL-17A, TNF-α, IL-1β, and iNOS) in brain tissues of mice and rats by real-time PCR. The result showed that brain inflammation in mice was more serious than in rats. Meanwhile, mRNA expression levels of IL-6, IL-1β, TNF-α, and iNOS increased after mice were infected. In contrast, mRNA levels of these cytokines in rats brain tissues decreased at post- infection 21 days. These cytokines mostly were secreted by activated microglia in central nervous system. Microglia of mice and rats were showed by Iba-1 (microglia marker) staining. In micee brains, microglia got together and had more significant activation than in rats brains. The results demonstrate that mice and rats have different CNS inflammation after infection by A. cantonensis, and it is in line with other researchers' reported findings. In conclusion, it is suggested that microglia activation is probably to be one of the most important factors in angiostrongyliasis from our study.

Chronic helminth infection and helminth-derived egg antigens promote adipose tissue M2 macrophages and improve insulin sensitivity in obese mice.

Chronic low-grade inflammation associated with obesity contributes to insulin resistance and type 2 diabetes. Helminth parasites are the strongest natural inducers of type 2 immune responses, and short-lived infection with rodent nematodes was reported to improve glucose tolerance in obese mice. Here, we investigated the effects of chronic infection (12 weeks) with Schistosoma mansoni, a helminth that infects millions of humans worldwide, on whole-body metabolic homeostasis and white adipose tissue (WAT) immune cell composition in high-fat diet-induced obese C57BL/6 male mice. Our data indicate that chronic helminth infection reduced body weight gain (-62%), fat mass gain (-89%), and adipocyte size; lowered whole-body insulin resistance (-23%) and glucose intolerance (-16%); and improved peripheral glucose uptake (+25%) and WAT insulin sensitivity. Analysis of immune cell composition by flow cytometry and quantitative PCR (qPCR) revealed that S. mansoni promoted strong increases in WAT eosinophils and alternatively activated (M2) macrophages. Importantly, injections with S. mansoni-soluble egg antigens (SEA) recapitulated the beneficial effect of parasite infection on whole-body metabolic homeostasis and induced type 2 immune responses in WAT and liver. Taken together, we provide novel data suggesting that chronic helminth infection and helminth-derived molecules protect against metabolic disorders by promoting a T helper 2 (Th2) response, eosinophilia, and WAT M2 polarization.

Membrane fractions from Strongyloides venezuelensis in the immunodiagnosis of human strongyloidiasis.

Strongyloides venezuelensis is a parasitic nematode of rodents frequently used to obtain heterologous antigens for the immunological diagnosis of human strongyloidiasis. The aim of this study was to evaluate membrane fractions from S. venezuelensis for human strongyloidiasis immunodiagnosis. Soluble and membrane fractions were obtained in phosphate saline (SS and SM) and Tris-HCl (TS and TM) from filariform larvae of S. venezuelensis. Ninety-two serum samples (n = 92) were obtained from 20 strongyloidiasis patients (Group I), 32 from patients with other parasitic diseases (Group II), and 40 from healthy individuals (Group III), and were analyzed by enzyme-linked immunosorbent assay (ELISA). Soluble fractions (SS and TS) showed 90.0% sensitivity and 88.9% specificity, whereas the membrane fractions (SM and TM) showed 95.0% sensitivity and 94.4% specificity. The present results suggest the possible use of membrane fractions of S. venezuelensis as an alternative antigen for human strongyloidiasis immunodiagnosis.

Genetic variability among Syphacia obvelata isolates from laboratory mice in four different geographical locations of China revealed by sequence analyses of five mitochondrial genes

Syphacia obvelata is a rodent nematode with high prevalence in laboratory mice. In the present study, we examined the genetic variability of S. obvelata from naturally infected laboratory mice in four different provinces, China. Five mitochondrial (mt) DNA regions, namely cytochrome c oxidase subunit 1 (pcox1), cytochrome b (pcytb), large subunit ribosomal RNA (prrnL) and NADH dehydrogenase subunits 1 and 5 (pnad1 and pnad5), were amplified separately from individual nematodes by PCR, and then sequenced directly. The size of the sequences of pcox1, pcytb, prrnL, pnad1 and pnad5 was 628 bp, 555 bp, 548 bp, 548 bp and 561 bp, respectively. While the intra-specific sequence variations within S. obvelata were 0–1.0% for pcox1, 0–1.6% for pcytb, 0–2.8% for prrnL, 0–2.0% for pnad1 and 0–1.8% for pnad5, the inter-specific sequence differences among members of the Oxyuridae were significantly higher, being 14.0–17.5% for pcox1, 27.5–32.9% for pcytb, 35.8–37.2% for prrnL, 22.2–26.8% for pnad1 and 22.3–25.2% for pnad5, respectively. Phylogenetic analyses based on combined sequences of four mt protein-coding genes, using Bayesian inference (BI), maximum likelihood (ML) and maximum parsimony (MP) methods, indicated that all of the S. obvelata samples grouped together with high statistical support, but samples from the same geographical origin did not always cluster together. These findings demonstrated the existence of low-level intra-specific variation in five mtDNA sequences among S. obvelata isolates from laboratory mice, but no obvious geographical distinction among S. obvelata isolates from laboratory mice in different geographic regions in China. These results provide basic information for further studies of systematics and population genetics of S. obvelata.

High throughput sequencing of the Angiostrongylus cantonensis genome: a parasite spreading worldwide

Angiostrongylus cantonensis is a parasitic nematode of rodents and a leading aetiological agent of eosinophilic meningitis in humans. Definitive diagnosis is difficult, often relying on immunodiagnostic methods which utilize crude antigens. New immunodiagnostic methods based on recombinant proteins are being developed, and ideally these methods would be made available worldwide. Identification of diagnostic targets, as well as studies on the biology of the parasite, are limited by a lack of molecular information on Angiostrongylus spp. available in databases. In this study we present data collected from DNA random high-throughput sequencing together with proteomic analyses and a cDNA walking methodology to identify and obtain the nucleotide or amino acid sequences of unknown immunoreactive proteins. 28 080 putative ORFs were obtained, of which 3371 had homology to other deposited protein sequences. Using the A. cantonensis genomic sequences, 156 putative ORFs, matching peptide sequences obtained from previous proteomic studies, were considered novel, with no homology to existing sequences. Full-length coding sequences of eight antigenic target proteins were obtained. In this study we generated not only the complete nucleotide sequences of the antigenic protein targets but also a large amount of genomic data which may help facilitate future genomic, proteomic, transcriptomic or metabolomic studies on Angiostrongylus.

Differences in microglia activation between rats-derived cell and mice-derived cell after stimulating by soluble antigen of IV larva from Angiostrongylus cantonensis in vitro

Angiostrongylus cantonensis is a rodent nematode. Adult worms of A. cantonensis live in the pulmonary arteries of rats. Humans and mice are accidental hosts or named nonpermissive hosts. The larva cannot develop into an adult worm and only causes serious eosinophilic meningitis or meningoencephalitis if humans or mice eat food containing larva of A. cantonensis in the third stage. The differing consequences largely depend on differing immune responses of the host to parasite during A. cantonensis invasion and development. Microglia is considered to be the key immune cell in the central nervous system like macrophage. To further understand the reasons for why mice and rats attain different outcomes in A. cantonensis infection, we set up the method to isolate and culture newborn rats' primary microglia and observe the activation of the microglia cells, comparing with mice microglia cell line N9. We treated cells with soluble antigen of the fourth larva of A. cantonensis (L4 larva) and measured mRNA levels of IL-1β, IL-5, IL-6, IL-13, eotaxin, iNOS, and TNF-α by real-time PCR. The results showed that N9 expressed high mRNA level of IL-6, IL-1β, TNF-α, iNOS, IL-5, IL-13, and eotaxin, but primary microglia only had IL-5, IL-13, and eotaxin mRNA level. It implies that microglia from rats and mice had different reaction to soluble antigen of A. cantonensis. Therefore, we supposed that microglia may play an immune modulation role during the brain inflammation induced by A. cantonensis.

The anthelmintic efficacy of papaya latex in a rodent–nematode model is not dependent on fasting before treatment

In earlier studies of the anthelmintic activity of plant cysteine proteinases (CPs), a period of food deprivation was routinely employed before administration of CPs, but there has been no systematic evaluation as to whether this does actually benefit the anthelmintic efficacy. Therefore, we assessed the effect of fasting on the efficacy of CPs from papaya latex (PL) against Heligmosomoides bakeri in C3H mice. We used a refined, supernatant extract of papaya latex (PLS) with known active enzyme content. The animals were divided into three groups (fasted prior to treatment with PLS, not fasted but treated with PLS and fasted but given only water). The study demonstrated clearly that although food deprivation had been routinely employed in much of the earlier work on CPs in mice infected with nematodes, fasting has no beneficial effect on the efficacy of PLS against H. bakeri infections. Administration of CPs to fed animals will also reduce the stress associated with fasting.

Gastric Spiruridiasis Caused byMastophorus murisin a Captive Population of Striped Possums (Dactylopsila trivirgata)

Striped possums (Dactylopsila trivirgata) are small arboreal marsupials for which limited medical information is known. Mastophorus muris is a gastric spirurid nematode of rodents that uses insects as intermediate hosts. Three cases of gastric spiruridiasis caused by M. muris in captive striped possums are reported for the first time. Diagnosis was made by the presence of adult nematodes in regurgitant and at necropsy. Low numbers of nematode ova shed intermittently in possum feces made evaluation of treatment success difficult. No histopathologic abnormalities were identified in one case. Control of M. muris in captive possum colonies may be achieved by interrupting the life cycle of the parasite.

Type 2 immune-inducing helminth vaccination maintains protective efficacy in the setting of repeated parasite exposures

Animal studies have demonstrated that helminth vaccines which induce type 2 immune responses can be protective. To date, however, such vaccines have not been tested against repeated parasite challenges. Since repeated antigenic challenge of patients with allergic disease results in immunologic tolerance, we hypothesized that a helminth vaccine which induces type 2 immune responses may lose its protective efficacy in the setting of repeated parasite exposures (RPEs). To test this hypothesis, we examined whether RPEs induce immunological tolerance and reduce the effectiveness of a type 2 immune-inducing vaccine. BALB/c mice vaccinated against Litomosoides sigmodontis, a filarial nematode of rodents, were repeatedly exposed to irradiated larvae for 2 or 8 weeks or to non-irradiated infectious larvae for three months. Vaccination-induced parasite-specific IgE levels, parasite antigen-driven basophil interleukin 4 (IL-4) release, and Th2 skewing of the cellular immune response remained stable in the face of RPEs. Furthermore, RPEs in vaccinated mice did not augment immunoregulatory responses, as parasite antigen-driven cellular proliferation, production of IL-10, and frequencies of CD4 +CD25 +FoxP3 + regulatory T-cells were not altered by RPEs. Challenge infections with infectious L3-stage larvae resulted in lower worm burdens in vaccinated mice given RPEs than in vaccinated controls. These results demonstrate that vaccines which induce type 2 immune responses can maintain their efficacy in the setting of repeated parasite exposures.

Syphacia obvelata modifies mitogen-activated protein kinases and nitric oxide synthases expression in murine bone marrow cells

Syphacia obvelata is a rodent nematode parasite with high prevalence in laboratory mice. In our previous work we have demonstrated that this gut-dwelling helminth induces significant hematopoietic changes, characterized by increased myelopoiesis and erythropoiesis in infected animals, and accompanied with altered reactivity of bone marrow hematopoietic progenitors to interleukin (IL)-17. In this study we extended these investigations by demonstrating that naturally acquired S. obvelata infection induces significant alterations in murine bone marrow cells manifested at the molecular level. Namely, S. obvelata infection induced sustained phosphorylation of the members of three major groups of distinctly regulated mitogen-activated protein kinases (MAPKs), the p38, the c-Jun amino-terminal kinase (JNK) and the extracellular signal-regulated kinase (ERK), as well as enhanced expression of mRNA for the inducible nitric oxide synthase (iNOS) in the bone marrow cells of infected animals. Furthermore, the infection interfered with the IL-17-mediated effects in bone marrow cells, since in normal mice IL-17 significantly enhanced phosphorylation of p38 MAPK and upregulated the expression of iNOS and the constitutive, endothelial (e)NOS mRNA, while in S. obvelata-infected animals IL-17 did not influence the MAPKs activation, but markedly down-regulated the expression of both NOS isoforms. The data obtained demonstrating that S. obvelata is able to manipulate signal transduction pathways in the hosts' bone marrow cells, pointed to the multiple layers of immunomodulatory ability of this pinworm parasite and highlighted the importance of working under pinworm-free conditions when using experimental murine models for immunohematopoietic investigations.