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IL-4 induces eotaxin: a possible mechanism of selective eosinophil recruitment in helminth infection and atopy.

A common feature of some parasitic infections and allergic and atopic skin diseases is the involvement of Th2 lymphocytes and the dermal appearance of eosinophils (Eos). Because Th2 lymphocytes apparently do not release Eo attractants, we addressed the question of whether the Th2 cytokine IL-4 induces its production in dermal fibroblasts. We therefore stimulated fibroblasts with IL-4. HPLC investigation of supernatants revealed a single Eo chemotactic protein, which was purified to homogeneity giving a single 13-kDa band upon SDS-PAGE analyses. Peptide mapping with subsequent amino acid sequencing revealed an Eo-selective chemotaxin, which consists of a mixture of N-terminally truncated and O-glycosylated forms of the chemokine eotaxin. Other chemokines such as RANTES, MCP-3, MCP-4, or MIP-1alpha were not detected as Eo chemotaxins under these conditions. Using reverse transcriptase-PCR techniques, we found that IL-4 dose and time dependently induces eotaxin mRNA in dermal fibroblasts. Stimulation with IL-4 and TNF-alpha caused a 10- to 20-fold increase of the release of three biochemically different eotaxin forms, each consisting of a mixture of N-terminally truncated and O-glycosylated variants having the same backbone amino acid sequence but different specific activities. Our findings support the hypothesis that eosinophil recruitment seen in IL-4-mediated skin reactions, at least in part, may be due to Th2 cytokine-mediated induction of eotaxin in dermal fibroblasts.

Amino Acid Sequence↗

Reduced protective efficacy of a blood-stage malaria vaccine by concurrent nematode infection.

Helminth infections, which are prevalent in areas where malaria is endemic, have been shown to modulate immune responses to unrelated pathogens and have been implicated in poor efficacy of malaria vaccines in humans. We established a murine coinfection model involving blood-stage Plasmodium chabaudi AS malaria and a gastrointestinal nematode, Heligmosomoides polygyrus, to investigate the impact of nematode infection on the protective efficacy of a malaria vaccine. C57BL/6 mice immunized with crude blood-stage P. chabaudi AS antigen in TiterMax adjuvant developed strong protection against malaria challenge. The same immunization protocol failed to induce strong protection in H. polygyrus-infected mice. Immunized nematode-infected mice produced significantly lower levels of malaria-specific antibody than nematode-free mice produced. In response to nematode and malarial antigens, spleen cells from immunized nematode-infected mice produced significantly lower levels of gamma interferon but more interleukin-4 (IL-4), IL-13, and IL-10 in vitro than spleen cells from immunized nematode-free mice produced. Furthermore, H. polygyrus infection also induced a strong transforming growth factor beta1 response in vivo and in vitro. Deworming treatment of H. polygyrus-infected mice before antimalarial immunization, but not deworming treatment after antimalarial immunization, restored the protective immunity to malaria challenge. These results demonstrate that concurrent nematode infection strongly modulates immune responses induced by an experimental malaria vaccine and consequently suppresses the protective efficacy of the vaccine against malaria challenge.

Adjuvants, Immunologic↗

Haematological and serological data from dogs raised worm-free and monospecifically infected with helminths.

Pups free from helminth infection were obtained by treating the bitch prior to parturition, and the bitch and her pups after whelping, with oxfendazole and praziquantel. They were then housed in an area free from contamination with helminth eggs. Freedom from infection was confirmed by necropsy examinations and by serological tests using the Enzyme Linked Immunosorbent Assay (ELISA). Groups of pups were infected with Toxocara canis, Echinococcus granulosus, Taenia ovis, T. pisiformis and T. hydatigena and bled at 5-day intervals. Haematological examinations and measurement of serum proteins were performed on blood samples obtained throughout 30 days of infection. Levels of serum proteins were not significantly altered in any infection. Pups infected with T. canis showed a marked increase in numbers of circulating eosinophils during the phase of larval migration through the liver and lungs; they also showed marked antibody responses to T. canis larval ES antigen. Haematological values were not significantly altered in any other pups.

Animals↗

The effect of birdsfoot trefoil (Lotus corniculatus) and chicory (Cichorium intybus) on parasite intensities and performance of lambs naturally infected with helminth parasites.

Conventionally, farmers rely upon the routine use of anthelmintics to control helminth parasites and their use has proved highly cost-effective. However, several factors, including the emergence of helminths resistant to pharmaceutical anthelmintics, are forcing farmers to seek alternative approaches to parasite control. Studies in New Zealand have shown that some alternative forages may reduce parasitic infestation in sheep. In the current study, it was found that under UK environmental conditions lambs with naturally acquired helminth infections grazing chicory (Cichorium intybus) and birdsfoot trefoil (Lotus corniculatus) had fewer helminth parasites than sheep grazing ryegrass/white clover (Lolium perenne/Trifolium repens). Twelve pure-bred Lleyn male lambs grazed replicated 0.5ha plots of birdsfoot trefoil, chicory or ryegrass/white clover for 5 weeks. Liveweight and faecal egg counts (FECs) were determined weekly and eight lambs per forage were slaughtered at the end of the trial to determine total helminth intensities. Lambs grazing birdsfoot trefoil had a lower FEC on day 7 (P<0.05) and fewer total adult helminths than those grazing the other forages on day 35 (P<0.01). Lambs grazing chicory did not have significantly lower FEC than lambs grazing other forages but these lambs were found to have fewer total adult abomasal helminths than lambs grazing ryegrass/white clover (P<0.001). As the performance of grazing lambs is inversely correlated with the intensity of helminth parasites, these alternative forages could be used to improve the liveweight gain of lambs produced in the UK. Overall, the results support the contention that alternative forages could have a positive role in the control of helminth parasites in sheep, subject to successful agronomic development and integration of these forages into whole farm systems.

Abomasum↗

The prevalence and intensity of infection with helminth parasites in Mus spretus from the Setubal Peninsula of Portugal.

The results of a 5 year study of helminth parasites of Mus spretus, are reported. Six nematode and 5 cestode species were identified but no helminth showed 100% prevalence in M. spretus, the most commonly encountered nematode and cestode species being Syphacia obvelata (46.6%) and Taenia taeniaeformis (22.4%). Among the more unusual helminth species identified was Eucoleus bacillatus, a capillariid nematode inhabiting the stomach musculature. This species was identified in 3 of the 5 years of the study. The results are discussed in the broader context of previous studies and the epidemiology of rodent helminth infections in general.

Animals↗

Immunological characteristics of patients infected with common intestinal helminths: results of a study based on reverse-transcriptase PCR.

To determine whether common helminth infections could modify the intestinal immunopathological status of the host, the expression in the human duodenal mucosa of cytokines, eosinophil- and mast-cell-specific molecules and monosaccharide transporters of the glucose-transporter (GLUT) family was explored. The 31 subjects were all patients at the gastro-intestinal disease unit of Nongkhai Hospital, Thailand. Four of the 10 patients who presented with eosinophilia (> or = 6.0% of their leucocytes were eosinophils), and five of the other 21 patients, had intestinal infections with helminths when they presented or within the previous 3 months. Studies based on semi-quantitative, reverse-transcriptase PCR revealed that the interleukin-5/interferon-gamma ratio was significantly higher in the noneosinophilic, helminth-infected patients than in the non-eosinophilic, uninfected patients, whereas the IgE receptor type I (Fc epsilon RI)/mast-cell tryptase ratio was significantly higher in the eosinophilic, helminth-infected patients than in the eosinophilic, uninfected patients. Expression of Charcot-Leyden-crystal protein, GLUT-1 and GLUT-5, however, showed no significant inter-group differences. Principal-components analysis of the data on eosinophils, interleukin-5, interferon-gamma, Fc epsilon RI and mast-cell tryptase revealed that one principal component could discriminate the patients who had helminth infection from the non-eosinophilic, uninfected patients, but not from the eosinophilic, uninfected patients. These results indicate that, whatever the intestinal pathology, patients infected with common intestinal helminths tend to develop a mucosal immunological response of the Th2 type.

Adult↗

Managing helminths of ruminants in organic farming.

The use of anthelmintics is strongly limited in organic farming. This may induce a change in the intensity (no of worms) and diversity (proportions of species) of helminth infection. Helminths remain a major preoccupation in organic sheep farming: high levels of infection have been recorded on several farms and helminth diversity is always higher. The helminth infection in milk cattle of northern Europe is controlled and diversity is higher in organic farms, as recorded in sheep. The role of helminth diversity on intensity is still unclear. Grazing management is one of the means to controlling helminths. The use of safe pastures for calves and sheep after weaning is one of the major components of control. The use of alternate or mixed grazing is common for cattle in northern countries but is uncommon for sheep in France. Grazing management is not sufficient to controlling infection in sheep and conventional anthelmintic treatments are performed. Additionally, alternative treatments are used. The alternative therapies based on phytotherapy or homeopathy are largely recommended in organic farming but do not have any demonstrated efficacy. More research is needed to evaluate such therapies.

Animal Husbandry↗

The role of IL-13 in helminth-induced inflammation and protective immunity against nematode infections.

Helminth infections induce the production of type 2 cytokines, which contribute both to expulsion of the worms and inflammatory responses that can either protect or damage the host. Although IL-4 has been considered the most critical cytokine for both inflammation and protective immunity, recent observations indicate that IL-13 - a related cytokine - can have equal or even greater importance than IL-4 in inflammatory responses and host protection against infection.

Animals↗

Infections and allergy - helminths, hygiene and host immune regulation.

There is increasing evidence that helminth infections can protect the host against Th2-mediated allergic pathologies, even though helminths themselves are strong Th2 inducers. In murine model systems, alleviation of allergy is not achieved through immune deviation to Th1, but is linked to expansion of regulatory T cell activity. Parasite infection does not prevent allergen sensitisation, but restricts the Th2 effector phase responsible for inflammation. Suppression of allergic inflammation can be transferred by Treg phenotype cells from an infected, allergen-naïve animal to an uninfected, sensitized recipient. Patent allergy in humans is also known to be modulated by helminth infections, suggesting that a similar regulatory network may be controlling immunopathologic disease in man.

Animals↗

Inverse association between skin response to aeroallergens and Schistosoma mansoni infection.

BACKGROUND: Helminthic infections and allergic disease are highly prevalent in many areas of the world. It is known that IgE antibodies are involved in the pathogenesis of both helminthiasis and atopy. However, the consequences of the presence of helminthic infections in atopic patients are still not completely understood. METHODS: Subjects infected by Schistosoma mansoni with more than 200 eggs/g of feces (n = 42) and uninfected subjects (n = 133) were selected from an endemic area of schistosomiasis. The history of allergy and results of the immediate hypersensitivity prick tests with inhalant allergen extracts were registered. Total IgE and IgE specific to S. mansoni and aeroallergens were measured in serum by ELISA. RESULTS: The proportion of individuals with a positive skin test to allergens was higher in the uninfected group (24.3%) than in the group with more than 200 eggs/g of feces (4.8%). The odds of atopy (defined as a positive test for at least one of the antigens) were 5 times higher (odds ratio = 7.0; 95% confidence interval = 1.6-31.1%; p = 0.01) in the uninfected group, after taking into account the potential influence of gender and age. While there was a tendency for higher total and S. mansoni-specific IgE levels in infected patients, an opposite trend, that is higher aeroallergen-specific IgE, was observed in uninfected subjects. CONCLUSIONS: There was a strong and statistically significant inverse association between the immediate skin test response to common aeroallergens and infection by S. mansoni. The results indicate that immediate hypersensitivity reactions may be suppressed in S. mansoni-infected individuals.

Adolescent↗

Infection of mice with the helminth Strongyloides stercoralis suppresses pulmonary allergic responses to ovalbumin.

Asthma and helminth infections induce similar immune responses characterized by the presence of peripheral blood eosinophilia and elevated serum IgE levels. Epidemiological surveys have reported either increases or decreases in the development of atopic diseases and asthma based on the prevalence of helminth infections in the population. The aim of this study was to determine if a pre-existing helminth infection would increase or decrease subsequent allergic responses to an unrelated allergen in the lungs. BALB/cByJ mice were infected with the nematode parasite Strongyloides stercoralis prior to ovalbumin (OVA) immunization and intratracheal challenge. Bronchoalveolar lavage (BAL) and fluid (BALF) were collected 3 days post-challenge and cellular and humoral immune responses were measured. Intracellular cytokine staining revealed increased IL-4 and IL-5 producing cells in BAL from mice infected with S. stercoralis before OVA sensitization. Increased IL-5 protein levels and decreased IFN-gamma protein levels were also observed in the BALF. There was, however, no increase in airway eosinophil accumulation in mice infectd with parasites before sensitization with OVA as compared to mice exposed to OVA alone. Furthermore, eotaxin levels in the lungs induced by OVA was suppressed in mice infected with the parasite before OVA sensitization. The development of OVA specific IgE responses in BALF was also impaired in mice infected with the parasite before sensitization with OVA. These results suggest that a pre-existing helminth infection may potentiate a systemic Type 2-type response yet simultaneously suppress in the lungs allergen-specific IgE responses and eotaxin levels in response to subsequent exposure to allergens.

Allergens↗

Th2 response polarization during infection with the helminth parasite Schistosoma mansoni.

T-helper 2 (Th2) cell responses play a critical role in protection against helminth infections. In the case of Schistosoma mansoni, an important helminth parasite of man, data from a mouse model of human disease have shown that Th2 responses are essential to allow host survival. In this infection, parasite eggs are the primary stimulus for Th2 response development. Recent work has shown that egg molecules exert multiple levels of control over the development of host interferon-gamma-associated inflammatory responses. Soluble egg antigen inhibits the ability of dendritic cells to make interleukin-12 and induces Th2-polarized adaptive immune responses that in combination with regulatory T-cell responses effectively limit Th1 response development. In this article, we discuss the factors influencing Th2 response polarization during infection with S. mansoni.

Animals↗

Co-infection of Onchocerca volvulus and intestinal helminths in indigenous and migrant farmers in southwest Ethiopia.

A cross-sectional survey on onchocerciasis and intestinal helminthic infections was conducted in two villages around the town of Teppi, south-west of Ethiopia on a total of 308 subjects of which 180 indigenous and 128 migrant settlers aged 10 years and above who lived in the area for at least 5 years. Of the total study subjects, 65% were males. The majority (64%) of the study subjects were in the age range of 21-40 years. The results of stool and skin snip examinations for ova/parasite and microfilaria revealed that, 62% (190) and 81% (248) of the study subjects were positive for intestinal parasites and microfilariderma respectively. Fifty percent (154) of the total subjects in the two villages had both onchocerciasis and intestinal helminthic infections. However, 80% (94/118) of the stool negative subjects also had onchocerciasis indicating that onchocercal skin infection has no significant influence on the acquisition of intestinal helminthic infections or vice versa [(relative risk 1.04, 95% CI 0.91, 1.18) P > 0.05]. Sixty-five percent (161/248) of the total skin snip positive individuals had microfilarial load of > 10 mf/mg of skin snip. The proportion of multiple infections with 2 or more intestinal helminthes was recorded in 51% (96/190) of individuals positive for intestinal parasitosis. There was a significant (x2 = 8.41, P < 0.005) difference in the onchocerciasis infection rate among indigenous (88%) and migrant (75%). No direct association was observed between onchocerciasis and intestinal parasitosis in the two study groups (indigenous and migrant settlers). The public health significance of coexistence of the two diseases, and the need for intensive control measures are discussed.

Adolescent↗

Eosinophilia in travelers.

Eosinophilia in travelers may be caused by infections acquired during travels. Infections with helminthic, but not protozoan, parasites are the most likely causes of eosinophilia, although other etiologies may warrant consideration. This article reviews the parasitic and other causes of eosinophilia. Helminthic infections early in their development may elicit the most pronounced eosinophilia yet be difficult to diagnose. Chronic helminthic infections may yield eosinophilia that persists for prolonged periods of time after initial infection.

Eosinophilia↗

Worms and allergy.

Worms and asthma are associated with a type 2 immune response, but evidence has accumulated that helminth infection is negatively associated with atopy, prevalence of allergic diseases and severity of asthma. One important difference between these polarized type 2 responses is that in allergy modulation of the immunological response is not appropriate, whereas in infection with helminths, several host mechanisms down-regulate the host immune response. As a result, patients infected with worms have a decrease in both type 1 and type 2 responses. The main mechanism involved in this down-modulation is increased production of IL-10, but expansion of regulatory T cells and NKT cells may also participate. Regarding the interaction between worms and allergy, a few variables need to be taken in account: phase (acute or chronic) of helminth infection, parasite load and species of helminth. In animals and humans, acute helminth infection may increase manifestations of allergy, whereas chronic infection with parasites decreases atopy. The modulation of the immune response by helminths is dependent on having an adequate parasite load. Moreover, although several helminth species have been shown to modulate immune responses, most in vitro and in vivo studies have focused on the importance of Schistosoma mansoni in down-modulating allergic reactions.

Animals↗

Health effect of wastewater reuse in agriculture.

The present study addresses the impact of wastewater reuse in agriculture on the transmission of protozoan and helminthic infections. For this purpose, an epidemiological study was carried out on two populations of children totalling 608 individuals for protozoan infections and 528 for helminthic infections. Each population comprised an exposed group living in the wastewater spreading area of Marrakech and a control group. Results showed that 72% of the exposed group had protozoan infections. This rate did not exceed 45% in the control group. The pathogenic protozoan infections observed were giardiasis and amoebiasis. Regarding helminthic infections, 73% of the exposed children were infected compared with 30% of the control group. The risk attributable to wastewater reuse in the transmission of pathogenic protozoan and helminthic infections was 41% and 43%, respectively. Children of the spreading area are therefore more exposed to detectable risks from parasitic helminths and protozoa than the control children.

Adolescent↗