Basophil-mediated protection against gastrointestinal helminths requires IgE-induced cytokine secretion

Schwartz, Christian; Turqueti-Neves, Adriana; Hartmann, Susanne; Yu, Philipp; Nimmerjahn, Falk; Voehringer, David

doi:10.1073/pnas.1412663111

Cited by 86 publications

(91 citation statements)

References 50 publications

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“…Yet, even if sterile immunity after vaccination with excretory secretory products from both tissue and adult stages of H. polygyrus bakeri was associated with high IgG1 titers, no protective IgG1 mAb has been identified to date (42,45). Very recently, it was shown that IgG1 is indeed dispensable for protection against challenge infection with Hpb (46). Thus, it is conceivable that the parasite induces a massive polyclonal, nonprotective IgG1 response, which may play a role in limiting fecundity (16) rather than targeting tissue-migrating larvae, whereas another isotype may activate MF-mediated cellular immunity against the helminth.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…Abnormalities in host responses to Brugia malayi , Heligmosomoides polygyrus , N. brasiliensis , T. spiralis and Schistosoma mansoni have been observed in these mice [35-38], indicating beneficial functions for IgE in these infections. Nevertheless, findings in IgE−/− mice are not always in accord with observations from experiments employing other approaches to manipulate levels of IgE or IgE signaling.…”

Section: The Role Of Ige In Parasite Immunitymentioning

confidence: 99%

“…However, because host-defense mechanisms often employ redundant or partially overlapping elements, it has been challenging to identify conclusive evidence that MCs, and particularly IgE-dependent MC activation, confer survival benefit to the host during parasite infection. In the case of infection with N. brasiliensis , basophils appear to play a more critical role than MCs in host resistance [38, 67, 68]. Studies in MC-deficient WBB6F 1 - Kit W/W-v mice indicate that MCs make little or no contribution to the expulsion of N. brasiliensis during primary infections with this nematode [69], whereas a modest defect in expulsion of N. brasiliensis was observed in MC-deficient C57BL/6- Kit W-sh/W-sh mice during primary but not secondary infections [68].…”

Section: The Roles Of Mast Cells In Parasite Immunitymentioning

confidence: 99%

IgE and mast cells in host defense against parasites and venoms

et al. 2016

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IgE-dependent mast cell activation is a major effector mechanism underlying the pathology associated with allergic disorders. The most dramatic of these IgE-associated disorders is the fatal anaphylaxis which can occur in some people who have developed IgE antibodies to otherwise innocuous antigens, such as those contained in certain foods and medicines. Why would such a highly “maladaptive” immune response develop in evolution, and be retained to the present day? Host defense against parasites has long been considered the only beneficial function that might be conferred by IgE and mast cells. However, recent studies have provided evidence that, in addition to participating in host resistance to certain parasites, mast cells and IgE are critical components of innate (mast cells) and adaptive (mast cells and IgE) immune responses that can enhance host defense against the toxicity of certain arthropod and animal venoms, including enhancing the survival of mice injected with such venoms. Yet, in some people, developing IgE antibodies to insect or snake venoms puts them at risk for having a potentially fatal anaphylactic reaction upon subsequent exposure to such venoms. Delineating the mechanisms underlying beneficial versus detrimental innate and adaptive immune responses associated with mast cell activation and IgE is likely to enhance our ability to identify potential therapeutic targets in such settings, not only for reducing the pathology associated with allergic disorders but perhaps also for enhancing immune protection against pathogens and animal venoms.

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“…Mast cell secretion of proteases has been shown to promote intestinal helminth expulsion by disrupting intestinal barrier function and larval killing of roundworm larvae through eosinophil recruitment (Lawrence et al, 2004;McDermott et al, 2003;Shin et al, 2008;Woodbury et al, 1984). As with most immunological functions, redundancies exist in antiparasite responses, and basophils provide complementary immunomodulatory and protective functions (Blankenhaus et al, 2014;Ohnmacht & Voehringer, 2010;Schwartz et al, 2014).…”

Section: Roles In Disease and Immunitymentioning

confidence: 99%