Susceptibility and immunity to helminth parasites

Maizels, Rick M.; Hewitson, James P.; Smith, Katherine A.

doi:10.1016/j.coi.2012.06.003

Cited by 178 publications

(163 citation statements)

References 65 publications

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“…During natural infection, a plethora of molecular mechanisms are applied by the host to trap, kill, or expel helminth parasites at various sites of infection (12,13). Protective immunity against most helminths is associated with a strong memory type 2 response, including the production of alternatively activated macrophages (MF) and class-switched Abs that can provide early protection against tissue-migrating larval stages (14)(15)(16).…”

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confidence: 99%

Antibody-Mediated Trapping of Helminth Larvae Requires CD11b and Fcγ Receptor I

Bieren

Volpe

Kulagin

et al. 2015

The Journal of Immunology

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Infections with intestinal helminths severely impact on human and veterinary health, particularly through the damage that these large parasites inflict when migrating through host tissues. Host immunity often targets the motility of tissue-migrating helminth larvae, which ideally should be mimicked by anti-helminth vaccines. However, the mechanisms of larval trapping are still poorly defined. We have recently reported an important role for Abs in the rapid trapping of tissue-migrating larvae of the murine parasite Heligmosomoides polygyrus bakeri. Trapping was mediated by macrophages (MΦ) and involved complement, activating FcRs, and Arginase-1 (Arg1) activity. However, the receptors and Ab isotypes responsible for MΦ adherence and Arg1 induction remained unclear. Using an in vitro coculture assay of H. polygyrus bakeri larvae and bone marrow–derived MΦ, we now identify CD11b as the major complement receptor mediating MΦ adherence to the larval surface. However, larval immobilization was largely independent of CD11b and instead required the activating IgG receptor FcγRI (CD64) both in vitro and during challenge H. polygyrus bakeri infection in vivo. FcγRI signaling also contributed to the upregulation of MΦ Arg1 expression in vitro and in vivo. Finally, IgG2a/c was the major IgG subtype from early immune serum bound by FcγRI on the MΦ surface, and purified IgG2c could trigger larval immobilization and Arg1 expression in MΦ in vitro. Our findings reveal a novel role for IgG2a/c-FcγRI–driven MΦ activation in the efficient trapping of tissue-migrating helminth larvae and thus provide important mechanistic insights vital for anti-helminth vaccine development.

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confidence: 99%

Antibody-Mediated Trapping of Helminth Larvae Requires CD11b and Fcγ Receptor I

Bieren

Volpe

Kulagin

et al. 2015

The Journal of Immunology

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“…Resistance to nematodes is defined as the ability of an animal to prevent the establishment of larvae in its gastrointestinal tract and eliminate parasites already established there (MAIZELS et al, 2012;TIZARD, 2008). Parasitological and immunological parameters (such as immunoglobulins, defense cells, and cytokines) are frequently used as markers for resistance.…”

Section: Discussionmentioning

confidence: 99%

Immune response of sheep naturally infected with Haemonchus spp. on pastures with two different nutritional conditions

Toscan

Cadore

Limana

et al. 2017

SCA

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Parasitic nematodes in the gastrointestinal tract of small ruminants are considered one of the main causes of economical and productive losses. Haemonchus contortus is characterized as the major parasite affecting sheep worldwide. This study was designed to evaluate immunological responses in sheep naturally infected with Haemonchus spp. in two different feed grounds: native and cultivated pasture. Fecal and blood samples were collected weekly from fifteen Corriedale sheep, ages 8 to 12 months, to determine the counting of eggs per gram of feces (EPG), and the concentration of haematocrit, eosinophils, and cytokines during an 84-day experiment. Bromatological analysis of the two pasture treatments (types) showed levels of crude protein and non-fibrous carbohydrates of 9.7% and 12.3% in the native pasture and 14.3% and 23.7% for the cultivated pasture, respectively. No significant difference in haematocrit concentration was found during the experiment between different pastures (p < 0.05). However, significant differences were found in EPG, eosinophils, interleukins, and immunoglobulins levels after 21 days in the cultivated (nutritionally-enhanced) pasture. These data suggest that immune response was characterized in sheep by significantly higher peripheral eosinophilia and an increase in serum concentrations of IgE, IgA, IgG, TNF-β, IFN-γ, and IL-6. Likewise, the improvement in forage condition resulted in a reduction of EPG and an increase of elements that improve a sheep's immune system response against Haemonchus spp. infection. Key words: Cytokines. Gastrointestinal nematode. Immunity. Protein diet. ResumoParasitas nematódeos do trato gastrointestinal de pequenos ruminantes são considerados uma das principais causas de perdas econômicas e produtivas. Haemonchus contortus é caracterizado como o parasita mais importante afetando ovinos em todo o mundo. Este estudo foi delineado para avaliar a resposta imunológica de ovinos naturalmente infectados com Haemonchus spp. em dois grupos alimentares diferentes: pastagem nativa e cultivada. Amostras de fezes e de sangue foram coletadas semanalmente de quinze ovinos Corriedale, com de 8 a 12 meses de idade, para determinar a contagem de ovos por grama de fezes (OPG), e a concentração do hematócrito, eosinófilos e citocinas durante 84 dias de experimento. Análises bromatológicas dos dois tratamentos de pastagens (tipos) demonstraram níveis de proteína bruta e carboidratos não-fibrosos de 9.7% e 12.3% na pastagem nativa e 14.3% e 23.7% para pastagem cultivada, respectivamente. Não foi encontrada diferença significativa na concentração do hematócrito durante o experimento entre as diferentes pastagens (p < 0,05). Entretanto, foram encontradas diferenças significativas no OPG, eosinófilos, interleucinas e níveis de imunoglobulinas depois de 21 na pastagem cultivada (melhorada nutricionalmente). Estes dados sugerem que a resposta imune em ovinos foi caracterizada por significativa elevação da eosinofilia periférica e aumento das concentrações séricas de IgE, IgA, I...

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“…40 It is increasingly believed that the rapid microfilarial clearance following ivermectin dosing results not from the direct impact of the drug but via suppression of the parasite's ability to evade the host's natural immune defense mechanism. [41][42][43][44][45][46][47][48][49] Immunomodulatory agents often display fewer side effects than drugs, as well as producing less opportunity for creation of resistance in target microorganisms, which helps explain the absence of drug resistance in humans.…”

Section: The Present: a Puzzlementioning

confidence: 99%

Ivermectin: enigmatic multifaceted ‘wonder’ drug continues to surprise and exceed expectations

2017

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Over the past decade, the global scientific community have begun to recognize the unmatched value of an extraordinary drug, ivermectin, that originates from a single microbe unearthed from soil in Japan. Work on ivermectin has seen its discoverer, Satoshi Ōmura, of Tokyo's prestigious Kitasato Institute, receive the 2014 Gairdner Global Health Award and the 2015 Nobel Prize in Physiology or Medicine, which he shared with a collaborating partner in the discovery and development of the drug, William Campbell of Merck & Co. Incorporated. Today, ivermectin is continuing to surprise and excite scientists, offering more and more promise to help improve global public health by treating a diverse range of diseases, with its unexpected potential as an antibacterial, antiviral and anti-cancer agent being particularly extraordinary.

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Susceptibility and immunity to helminth parasites

Cited by 178 publications

References 65 publications

Antibody-Mediated Trapping of Helminth Larvae Requires CD11b and Fcγ Receptor I

Antibody-Mediated Trapping of Helminth Larvae Requires CD11b and Fcγ Receptor I

Immune response of sheep naturally infected with Haemonchus spp. on pastures with two different nutritional conditions

Ivermectin: enigmatic multifaceted ‘wonder’ drug continues to surprise and exceed expectations

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