The relationship between circulating and intestinal <i>Heligmosomoides polygyrus</i>‐specific IgG<sub>1</sub> and IgA and resistance to primary infection

Ben-Smith, A.W.; Wahid, Faisal; Lammas, David A.; Behnke, Jerzy M.

doi:10.1046/j.1365-3024.1999.00236.x

Cited by 32 publications

(31 citation statements)

References 30 publications

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“…The clear difference in anti‐adult IgG1 levels, confirms earlier reports that adult worms induce a polyclonal B cell stimulation, with CBA mice, having the greater number of adult worms, showing the larger response (24). However, this finding contrasts with the results of earlier studies utilizing single pulse infections where the responder strains such as SWR, SJL and NIH were shown to have faster and more intense adult‐worm specific IgG1 responses (3,16). Furthermore, data exist to indicate that IgG1 antibodies to adult worms, in repeatedly infected mice, are host protective (25), raising the question as to why CBA were unable to control worms under the trickle infection protocol used here, given the intense IgG1 responses that were monitored.…”

Section: Discussioncontrasting

confidence: 97%

Cellular and serological responses in resistant and susceptible mice exposed to repeated infection with Heligmosomoides polygyrus bakeri

Behnke

Lowe

Clifford

et al. 2003

Parasite Immunology

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An experiment was carried out to compare the parasitological and immunological responses of SWR and CBA mice to trickle (repeated) infection with Heligmosomoides polygyrus. Male mice were given 125 L3 once per week and were killed in groups, together with naïve control mice, weekly until week 8. Worm burdens accumulated in CBA, stabilizing in week 5 in excess of 400 worms and remaining high until week 8. In contrast in SWR worm burdens peaked in week 3 at a mean worm burden of 129 and then fell sharply so that by week 6, despite continuing re-infection, no more worms were recovered from these mice. SWR mice showed a marked mast cell and mMCP-1 response, peaking in weeks 2-3, whereas in CBA mice these responses were slower, and even at their height in week 8 still less intense than those in SWR mice. Both strains responded initially with a very similar goblet cell response, which declined in SWR mice as worms were eliminated, but was sustained in CBA mice until week 8. Serum TNFalpha concentrations were higher in SWR mice throughout the experiment. Infection elicited strong serological responses against adult and L4 antigens in both SWR and CBA mice, involving all the isotypes tested (IgG1, IgA and IgE). Anti-L3 responses were examined only for IgG1. However, only two responses differed significantly between the strains: the IgE response to L4 antigens was more intense in SWR mice, and interestingly and unexpectedly, the IgG1 response to adult worm antigens was more intense in CBA mice. These results reflect the activation of predominantly Th2-driven effector mechanisms, that may be associated with host-protective immunity developing under the trickle infection protocol exploited in these experiments.

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Section: Discussioncontrasting

confidence: 97%

Cellular and serological responses in resistant and susceptible mice exposed to repeated infection with Heligmosomoides polygyrus bakeri

Behnke

Lowe

Clifford

et al. 2003

Parasite Immunology

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“…Many different strains were ranked in terms of their capacity to resist primary infections and to express acquired resistance , and therefore, it was possible now to correlate antibody responses with resistance across mouse strains of varying genotype and responder phenotype. Much as expected, it was soon found that good responder strains produced high levels of parasite‐specific IgG1, and poor responders much lower , and even within the strong/intermediate responder strains, IgG1 levels correlated negatively with worm burdens .…”

Section: Thirty‐five Years Agosupporting

confidence: 56%

“…However, consistent with the crucial role of antibodies in acquired resistance, faecal egg output differed markedly in secondary and tertiary infections with complete suppression of faecal egg counts in the lines bred for high antibody responses and in excess of 90% loss of worms . Inbred strains of mice that show poor antibody responses also harbour longer infections than those that respond more vigorously , but clearly, the role of antibodies needs to be investigated more thoroughly through the kinetics of worm rejection in wild‐type or genetically modified antibody‐deficient mice as has been done for challenge infections. This would be an important and exciting task for the near future given that antibodies might be expected to neutralize parasite products important in the modulation of the host immune response.…”

Section: Now In 2013mentioning

confidence: 90%

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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“…Specific IgG1 antibodies are known to be protective against H. polygyrus infection, 30 , 31 , 32 , 33 , 34 and their titer correlates with genetic resistance to this parasite 50 . We assayed serum antibody responses to parasite excretory–secretory products (termed HES) that are known to be the primary targets of serum antibodies in infected mice 51 .…”

Section: Resultsmentioning

confidence: 99%

Innate and adaptive type 2 immune cell responses in genetically controlled resistance to intestinal helminth infection

et al. 2014

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The nematode Heligmosomoides polygyrus is an excellent model for intestinal helminth parasitism. Infection in mice persists for varying lengths of time in different inbred strains, with CBA and C57BL/6 mice being fully susceptible, BALB/c partially so and SJL able to expel worms within 2–3 weeks of infection. We find that resistance correlates not only with the adaptive Th2 response, including IL-10 but with activation of innate lymphoid cell and macrophage populations. In addition, the titer and specificity range of the serum antibody response is maximal in resistant mice. In susceptible strains, Th2 responses were found to be counterbalanced by IFN-γ-producing CD4+ and CD8+ cells, but these are not solely responsible for susceptibility as mice deficient in either CD8+ T cells or IFN-γ remain unable to expel the parasites. Foxp3+ Treg numbers were comparable in all strains, but in the most resistant SJL strain, this population does not upregulate CD103 in infection, and in the lamina propria the frequency of Foxp3+CD103+ T cells is significantly lower than in susceptible mice. The more resistant SJL and BALB/c mice develop macrophage-rich IL-4Rα-dependent Type 2 granulomas around intestinal sites of larval invasion, and expression of alternative activation markers Arginase-1, Ch3L3 (Ym1) and RELM-α within the intestine and the peritoneal lavage was also strongly correlated with helminth elimination in these strains. Clodronate depletion of phagocytic cells compromises resistance of BALB/c mice and slows expulsion in the SJL strain. Thus, Type 2 immunity involves IL-4Rα-dependent innate cells including but not limited to a phagocyte population, the latter likely involving the action of specific antibodies.

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The relationship between circulating and intestinal Heligmosomoides polygyrus‐specific IgG₁ and IgA and resistance to primary infection

Cited by 32 publications

References 30 publications

Cellular and serological responses in resistant and susceptible mice exposed to repeated infection with Heligmosomoides polygyrus bakeri

Cellular and serological responses in resistant and susceptible mice exposed to repeated infection with Heligmosomoides polygyrus bakeri

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

Innate and adaptive type 2 immune cell responses in genetically controlled resistance to intestinal helminth infection

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The relationship between circulating and intestinal Heligmosomoides polygyrus‐specific IgG1 and IgA and resistance to primary infection

Cited by 32 publications

References 30 publications

Cellular and serological responses in resistant and susceptible mice exposed to repeated infection with Heligmosomoides polygyrus bakeri

Cellular and serological responses in resistant and susceptible mice exposed to repeated infection with Heligmosomoides polygyrus bakeri

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

Innate and adaptive type 2 immune cell responses in genetically controlled resistance to intestinal helminth infection

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The relationship between circulating and intestinal Heligmosomoides polygyrus‐specific IgG₁ and IgA and resistance to primary infection