Repeated infection of cats with<i>Brugia pahangi</i>: parasitological observations

Denham, D. A.; Medeiros, F.; Baldwin, Christopher; Kumar, Hemant; Midwinter, I.; Birch, D. W.; Smail, Amy

doi:10.1017/s0031182000063666

Cited by 24 publications

(17 citation statements)

References 9 publications

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“…In both humans and animal models, cryptic amicrofilaraemic infections can occur in which immunity appears to operate only against the microfilarial stage. For example, cats infected with B. pahangi often became Mf-negative and yet remained seropositive for circulating filarial antigen and were found to harbour live adult worms at autopsy [43]. Similarly, circulating antigen tests in humans identify a significant proportion of Mf-negative infected subjects.…”

Section: Discussionmentioning

confidence: 99%

The Secreted Triose Phosphate Isomerase of Brugia malayi Is Required to Sustain Microfilaria Production In Vivo

et al. 2014

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Human lymphatic filariasis is a major tropical disease transmitted through mosquito vectors which take up microfilarial larvae from the blood of infected subjects. Microfilariae are produced by long-lived adult parasites, which also release a suite of excretory-secretory products that have recently been subject to in-depth proteomic analysis. Surprisingly, the most abundant secreted protein of adult Brugia malayi is triose phosphate isomerase (TPI), a glycolytic enzyme usually associated with the cytosol. We now show that while TPI is a prominent target of the antibody response to infection, there is little antibody-mediated inhibition of catalytic activity by polyclonal sera. We generated a panel of twenty-three anti-TPI monoclonal antibodies and found only two were able to block TPI enzymatic activity. Immunisation of jirds with B. malayi TPI, or mice with the homologous protein from the rodent filaria Litomosoides sigmodontis, failed to induce neutralising antibodies or protective immunity. In contrast, passive transfer of neutralising monoclonal antibody to mice prior to implantation with adult B. malayi resulted in 60–70% reductions in microfilarial levels in vivo and both oocyte and microfilarial production by individual adult females. The loss of fecundity was accompanied by reduced IFNγ expression by CD4+ T cells and a higher proportion of macrophages at the site of infection. Thus, enzymatically active TPI plays an important role in the transmission cycle of B. malayi filarial parasites and is identified as a potential target for immunological and pharmacological intervention against filarial infections.

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Section: Discussionmentioning

confidence: 99%

The Secreted Triose Phosphate Isomerase of Brugia malayi Is Required to Sustain Microfilaria Production In Vivo

et al. 2014

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“…Despite development of resistance to additional infections, the majority of cats (70 to 75%) remain microfilaremic for years after repeated inoculations with L3 larvae (73,83). When cats do become amicrofilaremic, it can occur in three patterns: clearance of adult worms followed by gradual decline in microfilaria levels, dramatic drop in microfilaremia followed by slow decline in adult worm burden, and rapid clearance of MF with persistence of gravid adult females (83). Interestingly, worm-specific IgE is more commonly detected in cats that have cleared adult worms than in those with persistent infection (84).…”

Section: Morris Et Almentioning

confidence: 99%

A Comprehensive, Model-Based Review of Vaccine and Repeat Infection Trials for Filariasis

et al. 2013

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SUMMARY Filarial worms cause highly morbid diseases such as elephantiasis and river blindness. Since the 1940s, researchers have conducted vaccine trials in 27 different animal models of filariasis. Although no vaccine trial in a permissive model of filariasis has provided sterilizing immunity, great strides have been made toward developing vaccines that could block transmission, decrease pathological sequelae, or decrease susceptibility to infection. In this review, we have organized, to the best of our ability, all published filaria vaccine trials and reviewed them in the context of the animal models used. Additionally, we provide information on the life cycle, disease phenotype, concomitant immunity, and natural immunity during primary and secondary infections for 24 different filaria models.

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“…1992), and similar immunization can be attained by repeated infection with normal larvae (Denham et al . 1983, 1992, Eisenbeiss, Apfel & Meyer 1994), or by chemotherapeutically abbreviating infection before the patent stage (Grieve et al . 1988).…”

Section: Introductionmentioning

confidence: 99%

Antibody responses to filarial infective larvae are not dominated by the IgG4 isotype

Kurniawan

Sartono

Partònò

et al. 1998

Parasite Immunology

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The humoral immune response in humans to filarial parasites is generally dominated by the IgG4 isotype, when measured by ELISA against somatic adult worm extract. In contrast, as we report here, antibodies reactive to somatic extracts of infective larvae are more equally represented by IgG1 and IgG4. Moreover, binding to surface exposed epitopes in immunofluorescence on larval stages is mediated foremost by IgG1 and IgM, secondarily by IgG2 and IgG3, and very little by IgG4. Both anti-L3 surface and somatic antibodies are strongest in elephantiasis patients, and tend to increase with age. Antibody to the L3 surface is also present in most microfilaraemic individuals who bear no detectable antibodies to the surface of the microfilarial stage. These results demonstrate that a stage- and isotype-specific response is mounted to the L3 surface which should be considered as a possible mediator of concomitant immunity in filariasis.

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Repeated infection of cats withBrugia pahangi: parasitological observations

Cited by 24 publications

References 9 publications

The Secreted Triose Phosphate Isomerase of Brugia malayi Is Required to Sustain Microfilaria Production In Vivo

The Secreted Triose Phosphate Isomerase of Brugia malayi Is Required to Sustain Microfilaria Production In Vivo

A Comprehensive, Model-Based Review of Vaccine and Repeat Infection Trials for Filariasis

Antibody responses to filarial infective larvae are not dominated by the IgG4 isotype

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