Stimulation of immunity to <i>Nematospiroides dubius</i> in mice using larvae attenuated by cobalt 60 irradiation

Hagan, Paul; Behnke, Jerzy M.; Parish, Heather A.

doi:10.1111/j.1365-3024.1981.tb00393.x

Cited by 25 publications

(15 citation statements)

References 12 publications

(6 reference statements)

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“…Irradiated H. polygyrus larvae given orally stimulate protection against subsequent challenge [62, 145–148]. Notably, the efficacy of this irradiated larval vaccine is diminished by the coadministration of unirradiated larvae, indicating that the development of adult worms is able to inhibit development and/or expression of protective immunity against subsequent reinfection [146, 147].…”

Section: Vaccine-induced Immunitymentioning

confidence: 99%

Immunity to the model intestinal helminth parasite Heligmosomoides polygyrus

2012

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Heligmosomoides polygyrus is a natural intestinal parasite of mice, which offers an excellent model of the immunology of gastrointestinal helminth infections of humans and livestock. It is able to establish long-term chronic infections in many strains of mice, exerting potent immunomodulatory effects that dampen both protective immunity and bystander reactions to allergens and autoantigens. Immunity to the parasite develops naturally in some mouse strains and can be induced in others through immunization; while the mechanisms of protective immunity are not yet fully defined, both antibodies and a host cellular component are required, with strongest evidence for a role of alternatively activated macrophages. We discuss the balance between resistance and susceptibility in this model system and highlight new themes in innate and adaptive immunity, immunomodulation, and regulation of responsiveness in helminth infection.

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Section: Vaccine-induced Immunitymentioning

confidence: 99%

Immunity to the model intestinal helminth parasite Heligmosomoides polygyrus

2012

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“…Moreover, mice given curative anthelminthic treatment prior to adult maturation [21], or heavily irradiated infective larvae [22] develop protective immunity to challenge infection. Hence, as well as being a source of protective antigens, immature tissue-dwelling parasites actively contribute to immunological down-regulation, and we hypothesise that in the non-immune setting they are able to deflect or disable immune mechanisms within the gut tissue.…”

Section: Introductionmentioning

confidence: 99%

Secretion of Protective Antigens by Tissue-Stage Nematode Larvae Revealed by Proteomic Analysis and Vaccination-Induced Sterile Immunity

et al. 2013

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Gastrointestinal nematode parasites infect over 1 billion humans, with little evidence for generation of sterilising immunity. These helminths are highly adapted to their mammalian host, following a developmental program through successive niches, while effectively down-modulating host immune responsiveness. Larvae of Heligmosomoides polygyrus, for example, encyst in the intestinal submucosa, before emerging as adult worms into the duodenal lumen. Adults release immunomodulatory excretory-secretory (ES) products, but mice immunised with adult H. polygyrus ES become fully immune to challenge infection. ES products of the intestinal wall 4th stage (L4) larvae are similarly important in host-parasite interactions, as they readily generate sterile immunity against infection, while released material from the egg stage is ineffective. Proteomic analyses of L4 ES identifies protective antigen targets as well as potential tissue-phase immunomodulatory molecules, using as comparators the adult ES proteome and a profile of H. polygyrus egg-released material. While 135 proteins are shared between L4 and adult ES, 72 are L4 ES-specific; L4-specific proteins correspond to those whose transcription is restricted to larval stages, while shared proteins are generally transcribed by all life cycle forms. Two protein families are more heavily represented in the L4 secretome, the Sushi domain, associated with complement regulation, and the ShK/SXC domain related to a toxin interfering with T cell signalling. Both adult and L4 ES contain extensive but distinct arrays of Venom allergen/Ancylostoma secreted protein-Like (VAL) members, with acetylcholinesterases (ACEs) and apyrase APY-3 particularly abundant in L4 ES. Serum antibodies from mice vaccinated with L4 and adult ES react strongly to the VAL-1 protein and to ACE-1, indicating that these two antigens represent major vaccine targets for this intestinal nematode. We have thus defined an extensive and novel repertoire of H. polygyrus proteins closely implicated in immune modulation and protective immunity.

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“…The breakthrough came when it was realized that adult worms not only failed to induce effective resistance in many mouse strains and appeared not to be susceptible to mucosal responses in some strains of immune mice , but actually prevented the expression of host‐protective effector mechanisms operating at the mucosal level . The larval, tissue‐dwelling stages of this parasite are in fact highly immunogenic and can induce immunity even in poor responder strains of mice , as long as the period of residence of adult worms in the gut lumen is brief, as for example after infection with irradiated infective larvae , following treatment with ivermectin, which kills the larvae in situ in the intestinal walls , or by chemotherapy immediately after their emergence from the intestinal walls 7–9 days post‐infection . It was shown that an average of just over 3 infective larvae per mouse was sufficient to generate an 84% reduction in challenge infection worm burdens in NIH mice when the immunizing larvae were killed by ivermectin on day 6 post‐infection .…”

Section: Thirty‐five Years Agomentioning

confidence: 99%

Understanding the role of antibodies in murine infections with Heligmosomoides (polygyrus) bakeri: 35 years ago, now and 35 years ahead

Harris

Pleass

Behnke

2014

Parasite Immunology

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SUMMARYThe rodent intestinal nematode H.p.bakeri has played an important role in the exploration of the host-parasite relationship of chronic nematode infections for over six decades, since the parasite was first isolated in the 1950s by Ehrenford. It soon became a popular laboratory model providing a tractable experimental system that is easy to maintain in the laboratory and far more cost-effective than other laboratory nematode-rodent model systems. Immunity to this parasite is complex, dependent on antibodies, but confounded by the parasite's potent immunosuppressive secretions that facilitate chronic survival in murine hosts. In this review, we remind readers of the state of knowledge in the 1970s, when the first volume of Parasite Immunology was published, focusing on the role of antibodies in protective immunity. We show how our understanding of the host-parasite relationship then developed over the following 35 years to date, we propose testable hypotheses for future researchers to tackle, and we speculate on how the new technologies will be applied to enable an increasingly refined understanding of the role of antibodies in host-protective immunity, and its evasion, to be achieved in the longer term.

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Stimulation of immunity to Nematospiroides dubius in mice using larvae attenuated by cobalt 60 irradiation

Cited by 25 publications

References 12 publications

Immunity to the model intestinal helminth parasite Heligmosomoides polygyrus

Immunity to the model intestinal helminth parasite Heligmosomoides polygyrus

Secretion of Protective Antigens by Tissue-Stage Nematode Larvae Revealed by Proteomic Analysis and Vaccination-Induced Sterile Immunity

Understanding the role of antibodies in murine infections with Heligmosomoides (polygyrus) bakeri: 35 years ago, now and 35 years ahead

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