Genetic control of immunity to <i>Nematospiroides dubius</i>: a 9‐day anthelmintic abbreviated immunizing regime which separates weak and strong responder strains of mice

Behnke, Jerzy M.; Robinson, Michael B.

doi:10.1111/j.1365-3024.1985.tb00073.x

Cited by 94 publications

(99 citation statements)

References 23 publications

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“…The study reported in this paper was necessary to provide us with data on optimal doses of ivermectin. The adult stages of H. polygyrus are immunosuppressive in the mouse (Behnke, 1987 ) whilst the larval stages provide the antigenic stimulus, which in responder strains results in the development of acquired immunity (Jacobson et al, 1982;Behnke and Robinson, 1985). The larvae of H. polygyrus develop for 8-10 days in the muscularis externa and undergo a moult during this period.…”

Section: Discussionmentioning

confidence: 99%

“…The tissue stages of H. polygyrus (1-8 days post infection) are hardly affected by pyrantel and the drug cannot be used to terminate infections earlier than 10-14 days post infection (Behnke and Wakelin, 1977;Behnke and Robinson, 1985 ). Nevertheless, there is evidence that the earlier stages are immunogenic, particularly L4 and hence there is a requirement for drugs that show high efficacy against the tissue-dwelling larval stages ofH.…”

Section: Introductionmentioning

confidence: 99%

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Factors affecting the efficacy of ivermectin against Heligmosomoides polygyrus (Nematospiroides dubius) in mice

Wahid

Behnke

Conway

1989

Veterinary Parasitology

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A note on versions:The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription.For more information, please contact eprints@nottingham.ac.uk Veterinary Parasitology, 32 (1989) The efficacy of ivermectin against Heligmosomoides polygyrus was investigated in 5 mouse strains (CFLP, NIH, C57Bllo, BALB/c and CBA ) using a variety of dose levels, and subcutaneous and oral administration, Heligmosomoides polygyrus were not completely eliminated when 5 mg kg 1 of ivermectin was given 6 days after infection, but 10 mg kg-~ was totally effective. Significant mouse-strain variation in drug efficacy was detected, NIH mice requiring treatment with higher doses than CFLP mice in order to bring about a comparable level of larvicidal activity. Ivermectin was more effective when given subcutaneously than when given orally, regardless of the dose administered or the strain of mouse tested. The anthelmintic effect of the treatment was more persistent in CFLP mice given 20 mg kg-~ subcutaneously than in NIH mice or in mice treated orally, and a 20-day interval between administration and infection was insufficient to prevent inhibition of parasite survival. Ivermectin was shown to be totally effective at 20 mg kg-1 given subcutaneously in killing immune arrested larvae of H. polygyrus.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Factors affecting the efficacy of ivermectin against Heligmosomoides polygyrus (Nematospiroides dubius) in mice

Wahid

Behnke

Conway

1989

Veterinary Parasitology

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“…The first inbred strain to show an unusually high level of resistance to challenge was a little-known strain called NIH (Behnke and Wakelin, 1977), but even this strain was not able to remove primary infection adult worms easily (Behnke and Robinson, 1985). Cypess et al (1977) reported on a hybrid strain (LAF1) able to clear up to 50 % of adult worms by 3 weeks after infection, and Prowse et al (1979) and Mitchell et al (1982) identified the inbred SJL strain as one that removes adult worm infections rapidly, in contrast to other mouse strains.…”

Section: G E N E T I C S O F T H E H O S T R E S P O N S E T O C H R mentioning

confidence: 99%

Heligmosomoides bakeri: a model for exploring the biology and genetics of resistance to chronic gastrointestinal nematode infections

2009

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A note on versions:The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription. The intestinal nematode Heligmosomoides bakeri has undergone 2 name changes during the last 4 decades. Originally, the name conferred on the organism in the early 20th century was Nematospiroides dubius, but this was dropped in favour of Heligmosomoides polygyrus, and then more recently H. bakeri, to distinguish it from a closely related parasite commonly found in wood mice in Europe. H. bakeri typically causes long-lasting infections in mice and in this respect it has been an invaluable laboratory model of chronic intestinal nematode infections. Resistance to H. bakeri is a dominant trait and is controlled by genes both within and outside the MHC. More recently, a significant QTL has been identified on chromosome 1, although the identity of the underlying genes is not yet known. Other QTL for resistance traits and for the accompanying immune responses were also defined, indicating that resistance to H. bakeri is a highly polygenic phenomenon. Hence marker-assisted breeding programmes aiming to improve resistance to GI nematodes in breeds of domestic livestock will need to be highly selective, focussing on genes that confer the greatest proportion of overall genetic resistance, whilst leaving livestock well-equipped genetically to cope with other types of pathogens and preserving important production traits.

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“…Most helminth parasites are long-lived and, in general, cause chronic infections (3,30). However, the immune mechanism(s) underlying the chronicity of helminth infection is not fully understood.…”

Section: Vol 73 2005 Modulation Of Antimalarial Immunity By Nematodmentioning

confidence: 99%

“…H. polygyrus is a murine nematode parasite that dwells in the small intestine of the host. In most inbred strains of mice, H. polygyrus establishes a chronic primary infection, which lasts for several months (3,30). Infection with this nematode parasite induces a strong Th2 immune response characterized by production of the cytokines interleukin-4 (IL-4), IL-5, and IL-13, immunoglobulin E (IgE) and IgG1 antibodies, eosinophilia, and mastocytosis in intestinal mucosal tissue (14,15,20,22).…”

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confidence: 99%

Impairment of Protective Immunity to Blood-Stage Malaria by Concurrent Nematode Infection

et al. 2005

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Helminthiases, which are highly prevalent in areas where malaria is endemic, have been shown to modulate or suppress the immune response to unrelated antigens or pathogens. In this study, we established a murine model of coinfection with a gastrointestinal nematode parasite, Heligmosomoides polygyrus, and the blood-stage malaria parasite Plasmodium chabaudi AS in order to investigate the modulation of antimalarial immunity by concurrent nematode infection. Chronic infection with the nematode for 2, 3, or 5 weeks before P. chabaudi AS infection severely impaired the ability of C57BL/6 mice to control malaria, as demonstrated by severe mortality and significantly increased malaria peak parasitemia levels. Coinfected mice produced significantly lower levels of gamma interferon (IFN-␥) during P. chabaudi AS infection than mice infected with malaria alone. Concurrent nematode infection also suppressed production of type 1-associated, malaria-specific immunoglobulin G2a. Mice either infected with the nematode alone or coinfected with the nematode and malaria had high transforming growth factor ␤1 (TGF-␤1) levels, and concurrent nematode and malaria infections resulted in high levels of interleukin-10 in vivo. Splenic CD11c ؉ dendritic cells (DC) from mice infected with malaria alone and coinfected mice showed similarly increased expression of CD40, CD80, and CD86, but DC from coinfected mice were unable to induce CD4 ؉ T-cell proliferation and optimal IFN-␥ production in response to the malaria antigen in vitro. Importantly, treatment of nematode-infected mice with an anthelmintic drug prior to malaria infection fully restored protective antimalarial immunity and reduced TGF-␤1 levels. These results demonstrate that concurrent nematode infection strongly modulates multiple aspects of immunity to bloodstage malaria and consequently impairs the development of protective antimalarial immunity.

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Genetic control of immunity to Nematospiroides dubius: a 9‐day anthelmintic abbreviated immunizing regime which separates weak and strong responder strains of mice

Cited by 94 publications

References 23 publications

Factors affecting the efficacy of ivermectin against Heligmosomoides polygyrus (Nematospiroides dubius) in mice

Factors affecting the efficacy of ivermectin against Heligmosomoides polygyrus (Nematospiroides dubius) in mice

Heligmosomoides bakeri: a model for exploring the biology and genetics of resistance to chronic gastrointestinal nematode infections

Impairment of Protective Immunity to Blood-Stage Malaria by Concurrent Nematode Infection

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