Helminth products bypass the need for TSLP in Th2 immune responses by directly modulating dendritic cell function

Massacand, Joanna; Stettler, Rebecca; Meier, Reto; Humphreys, Neil; Grencis, Richard K.; Marsland, Benjamin J.; Harris, Nicola L.

doi:10.1073/pnas.0906367106

Cited by 160 publications

(177 citation statements)

References 44 publications

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“…Whereas neurons relay their signals via the neurotransmitter neuromedin U, 23 14,32,33 that strongly synergize and prompt the release of IL-4, IL-5, IL-9, and IL-13 from various sources, notably type 2 innate lymphoid cells (ILC2). [15][16][17]25,[34][35][36][37][38] Epithelium-derived IL-25 and IL-33, in particular, are important for driving IL-5 and IL-13 production from ILC2, the latter of which induces a number of responses, including goblet and tuft cell expansion, resulting in a strong positive feedback loop with increased production of IL-25 by epithelial cells.…”

Section: Transmissionmentioning

confidence: 99%

“…29 The data on TSLP during parasite infections are sparse, but unlike IL-25 and IL-33, which are critical for the expulsion of multiple parasites, TSLP appears to be involved only during T. muris but not N. brasiliensis or H. polygyrus infections, 14,32,33 and this is understandable given that TSLP is mainly expressed in the large intestine. 33 TSLP can be directly recognized by dendritic cells 54 as well as basophils, 55 again suggesting that epithelial-derived cytokines can bypass ILC2.…”

Section: Transmissionmentioning

confidence: 99%

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Immunity to gastrointestinal nematode infections

2018

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Section: Transmissionmentioning

confidence: 99%

Section: Transmissionmentioning

confidence: 99%

Immunity to gastrointestinal nematode infections

2018

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“…Quantitative real-time PCR was performed, as described previously (23), using the following primers: GAPDH, sense, 59-GGGTGTGAACCAC-GAGAAAT-39 and antisense, 59-CCTTCCACAATGCCAAAGTT-39; Arg1, sense, 59-GCAACCTG TGTCCTTTCTCC-39 and antisense, 59-TCTACG-TCTCGCAAGCCAAT-39.…”

Section: Quantitative Real-time Pcrmentioning

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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“…Interestingly, while excretorysecretory products (ES) from the latter three worms suppress production of IL-12 by DC, ES from T. muris fails to do so [28,61]. This suggests that helminth-elicited TSLP plays a nonredundant role in priming Th2 responses via DC in infections where DC are not modulated by helminth-derived products, while it is possible to bypass the need for TSLP during infections where DC are able to recognize and respond to helminth-derived factors directly.…”

Section: Modulation Through Prr-signaling Independent Mechanismsmentioning

confidence: 99%

Helminths and dendritic cells: Sensing and regulating via pattern recognition receptors, Th2 and Treg responses

et al. 2010

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The classical reaction of the host to helminth infections is the induction of Th2 immune responses with a regulatory component. DC, as central players in the induction and maintenance of immune responses, play a prominent role in both these processes, and in recent years considerable progress has been made in elucidating the mechanisms behind the interplay between DC and helminths. It is becoming increasingly clear that helminths modulate DC function not only via direct interactions but also indirectly via host-derived cues. Furthermore, while studies have until recently focused on receptor signalingmediated DC modulation by helminths, evidence is emerging that DC may also respond to helminth infections by sensing stress signals or tissue damage inflicted by the worms or their products. Here, we will discuss these new insights and will link them to the origin and importance of Th2 and regulatory immune responses with respect to the survival of both parasite and host.Key words: DC . Helminth . Th cell polarization . Tissue damage IntroductionThe classical reaction of the host to helminth infections is the induction of Th2 responses. The induction of Th2 immunity has been shown to be important for resistance to helminth infections in various model systems; however, despite induction of a Th2 response, total clearance of the parasites rarely occurs in man (reviewed in [1,2]). This implies that helminths have evolved strategies, such as evasion or suppression of the host immune response that prevent their expulsion and permit their long-term survival. The immune modulatory effects are thought to arise from the helminth's capacity to exploit the host's own system of immune regulation, which is normally crucial for the maintenance of immune homeostasis and self tolerance. In this respect, the induction of Treg has been shown to be one of the most common mechanisms that restrains immune responses against the parasite while also preventing excessive inflammation and tissue damage inflicted by the worms (reviewed in [2,3]). Therefore, it is not surprising that among the variety of mechanisms developed by helminths to influence host immune responses, modulation of DC as pivotal players in the initiation and polarization of adaptive immune responses, including Treg modulation, may have a particularly important role (reviewed in [2,4,5] ) carbohydrate epitope found in schistosoma soluble egg antigens (SEA), has been implicated in TLR4-dependent priming of Th2 responses via DC [9]. However, SEA is also known to be capable of modulating DC for Th2 priming in the absence of TLR signaling [10]. Furthermore, phosphatidylserine (PS) lipids derived from schistosomes and ascaris worms, which carry TLR2-activating molecules, have been shown to promote Th2 responses via DC, but this is not TLR2 dependent [11], whereas monoacetylated PS lipids from schistosomes were found to specifically instruct DC to preferentially induce IL-10-producing Treg in a TLR2-dependent fashion [12]. Although TLR2 does not seem to be essential for Th2 polar...

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Helminth products bypass the need for TSLP in Th2 immune responses by directly modulating dendritic cell function

Abstract: Thymic stromal lymphopoietin (TSLP) is an interleukin (IL)-

Cited by 160 publications

References 44 publications

Immunity to gastrointestinal nematode infections

Immunity to gastrointestinal nematode infections

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

Helminths and dendritic cells: Sensing and regulating via pattern recognition receptors, Th2 and Treg responses

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