The Mast Cell and Gut Nematodes: Damage and Defence

Pennock, Joanne L.; Grencis, Richard K.

doi:10.1159/000088885

Cited by 56 publications

(54 citation statements)

References 52 publications

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“…The fecundity of Heligneosomoides polygyrus was higher in mast cell-deficient mice than in wild-type controls (54). However, these studies indicate that the mast cell phenotype is important in driving Th2 immunity that is essential for clearing gut parasites (55). We previously showed that mast cell number increases markedly in the peritoneal cavity and liver of F. hepatica-infected and FhTeg-injected mice and that the interaction of FhTeg with mast cells does not promote Th2 immune response or suppress IgE-mediated mast cell activation (56).…”

Section: Discussionmentioning

confidence: 82%

Fasciola hepatica Tegumental Coat Impairs Mast Cells’ Ability To Drive Th1 Immune Responses

Vukman

Adams

Metz

et al. 2013

The Journal of Immunology

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The parasitic worm Fasciola hepatica induces strong Th2 and T-regulatory immune responses while simultaneously suppressing Th1-driven immune responses to bystander microbial infections. It also prevents the initiation of Th1-mediated autoimmune disorders in mice through the suppression of Th17 and Th1 immune responses, and this can be mimicked by parasite-derived molecules. We have isolated F. hepatica tegumental coat Ag (FhTeg) and demonstrated its suppressive effect in vivo by directly targeting dendritic cells, impairing their ability to drive Th1 responses. Mast cells are critical in promoting Th1 protective immunity during bacterial infection and in driving Th1-mediated pathological conditions in autoimmune diseases. In this article, we show that FhTeg inhibits the ability of mast cells to drive the Th1 immune response by suppressing cytokine secretion (TNF-α, IL-6, IFN-γ, and IL-10) and ICAM1 expression in mast cells stimulated with LPS or heat-inactivated Bordetella pertussis Ag. These heat-inactivated B. pertussis Ag/LPS–stimulated mast cells fail to promote Th1 immune responses in CD4+ T cells when pretreated with FhTeg, and a role for ICAM1 in this process was demonstrated. FhTeg suppresses the activation of transcription factors in the TLR signaling pathway, which explains the decrease in cytokine production and cell surface marker expression. We demonstrated that FhTeg suppresses MAPK and NF-κB activation and enhances SOCS3 expression, which could explain its negative effect on the TLR pathways. We conclude that FhTeg targets innate immune cells, inhibiting their ability to drive Th1 immune responses.

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Section: Discussionmentioning

confidence: 82%

Fasciola hepatica Tegumental Coat Impairs Mast Cells’ Ability To Drive Th1 Immune Responses

Vukman

Adams

Metz

et al. 2013

The Journal of Immunology

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“…In searching for protective MC functions, mucosal MC activation through IgE was found to be involved in the expulsion of parasitic gastrointestinal helminths. 6 The 'innate face' of MCs 7 is based on the broad range of receptors that allow the stimulation of MCs independent of IgE. 8 The receptor repertoire includes numerous pattern recognition receptors (PRRs), which encompass most Toll-like receptors (TLRs), including TLR3 and TLR9.…”

Section: Introductionmentioning

confidence: 99%

“…Surprisingly, the data revealed two waves of MC activation and degranulation: a first wave indirectly depending on TLR3/TRIF signaling followed by a second wave associated with direct infection of MCs but not involving TLR3/TRIF signaling. MC-deficient Kit W-sh/W-sh mice were MCs reconstituted by the transfer of bone marrow-derived MCs (BMMCs) generated from either WT C57BL/6 mice or B6-congenic TLR3 2/2 mice as described previously, 18 except that, to achieve accelerated MC reconstitution preferentially in the peritoneum, 3310 6 BMMC/500 ml PBS per mouse was transferred intraperitoneally, and MC degranulation experiments were performed 5 weeks later. 31 Measurement of in vivo virus-induced MC degranulation WT C57BL/6 mice, B6-congenic mice with gene knockouts affecting TLR3/TRIF or MyD88 signaling, and MC-reconstituted B6-congenic Kit W-sh/W-sh mice were infected intraperitoneally with 10 6 PFU/100 ml PBS of mouse embryo fibroblast cell culturepropagated, sucrose gradient-purified, bacterial artificial chromosome-derived viruses 32,33 (i) mCMV MW97.01, 34 here, briefly referred to as mCMV; (ii) mutant virus mCMV-Dm157 lacking the ligand of the activating NK cell receptor Ly49H; 35 (iii) constitutive reporter virus mCMV-gfp; 36 and (iv) conditional reporter virus mCMV-Dm157-flox-egfp.…”

Section: Introductionmentioning

confidence: 99%

Mast cells as rapid innate sensors of cytomegalovirus by TLR3/TRIF signaling-dependent and -independent mechanisms

et al. 2014

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The succinct metaphor, 'the immune system's loaded gun', has been used to describe the role of mast cells (MCs) due to their storage of a wide range of potent pro-inflammatory and antimicrobial mediators in secretory granules that can be released almost instantly on demand to fight invaders. Located at host-environment boundaries and equipped with an arsenal of pattern recognition receptors, MCs are destined to be rapid innate sensors of pathogens penetrating endothelial and epithelial surfaces. Although the importance of MCs in antimicrobial and antiparasitic defense has long been appreciated, their role in raising the alarm against viral infections has been noted only recently. Work on cytomegalovirus (CMV) infection in the murine model has revealed MCs as players in a novel cross-talk axis between innate and adaptive immune surveillance of CMV, in that infection of MCs, which is associated with MC degranulation and release of the chemokine CCL5, enhances the recruitment of protective CD8 T cells to extravascular sites of virus replication, specifically to lung interstitium and alveolar epithelium. Here, we have expanded on these studies by investigating the conditions for MC activation and the consequent degranulation in response to host infection. Surprisingly, the data revealed two temporally and mechanistically distinct waves of MC activation: an almost instant indirect activation that depended on TLR3/TRIF signaling and delayed activation by direct infection of MCs that did not involve TLR3/TRIF signaling. Cell type-specific Cre-recombination that yielded eGFP-expressing reporter virus selectively originating from MCs identified MC as a new in vivo, first-hit target cell of productive murine CMV infection.

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“…(Li et al, 2012). Integrins, particularly integrin β-7, play a key role in the accumulation of mast cells in the gastrointestinal mucosa (Pennock and Grencis, 2006). Lectins are thought to be mediators of inflammation that enhance immune response (Lasky, 1991).…”

Section: Cell Adhesion Moleculesmentioning

confidence: 99%

“…In such cases, eosinophils immobilized H. contortus larvae in the presence of anti-Haemonchus antibodies in an in vitro study (Rainbird et al, 1998;Shakya et al, 2011). According to Pennock and Grencis (2006), post infection mastocytosis had an important role in elimination of the specific parasite in lambs. A greater number of eosinophils and mucosal mast cells in Native exists, it is presumed that the biologically active antibody is secretory IgA, which is actively secreted across the mucosal epithelium of the abomasum (Macpherson et al 2008;Venturina et al, 2013).…”

Section: The Role Of Immunoglobulin a (Iga) And Immunoglobulin E (Ige)mentioning

confidence: 99%

Immune and other factors modulating host resistance against gastrointestinal nematode parasites in sheep

Arsenopoulos

Symeonidou

Papadopoulos

2018

J Hellenic Vet Med Soc

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Infection of small ruminants with gastrointestinal nematode (GIN) parasites is a significant problem with crucial impact on meat and milk production. The strategy of administrating anthelminthic drugs has been implemented for many years and has resulted in the development of resistant strains of parasites. Meanwhile, consumers demand for free of drugs products have led to the adoption of alternative control methods, which involve the selective breeding of animals, which are resistant to parasitism. The development of immunity and therefore, resistance against gastrointestinal parasites is based on the activation of specific host genes. Gene analysis has revealed areas (QTLs), which affect resistance or susceptibility of sheep to gastrointestinal infestations between animals of different breeds and between individuals of the same breed. The role of cytokines and T helper cells has been enhanced as research, strongly, supports the connection of Th2 cells with resistance and Th1 cells with susceptibility against GIN. Latest data implicates T regulatory cells and a specific cell type, Th17, in immune response mechanisms. Specific adhesion molecules (integrins, lectins, cadherins) are produced in the gut lumen in sufficient amounts and appear to boost immunity and reduce clinical signs in sheep. Additionally, the immunoglobulins IgA and IgE have been positively correlated with increased resistance against GIN. In several cases of GIN, where an increased number of eosinophils and mast cells in the intestinal epithelium have been recorded, the animals had a reduced number of parasite eggs in their feces. The genes of the Major Histocompatibility Complex have been referred to as potential resistance or susceptibility markers. Other enzymes, like chitinases, enhance the resilience of animals and protect them effectively. Animal’s nutritional status is another determinant factor of immune capability against GIN in sheep, both systemic, as well as locally. Regarding the effect of reactive oxygen and nitrogen species, some researchers support their direct effect against GIN, resulting in a natural reduction of their number, while others claim the indirect action in the intestinal epithelium by reducing local immunity. Consequently, the detection of genes associated with resistance or susceptibility to gastrointestinal infestations is promising and in line with modern requirements.

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The Mast Cell and Gut Nematodes: Damage and Defence

Cited by 56 publications

References 52 publications

Fasciola hepatica Tegumental Coat Impairs Mast Cells’ Ability To Drive Th1 Immune Responses

Fasciola hepatica Tegumental Coat Impairs Mast Cells’ Ability To Drive Th1 Immune Responses

Mast cells as rapid innate sensors of cytomegalovirus by TLR3/TRIF signaling-dependent and -independent mechanisms

Immune and other factors modulating host resistance against gastrointestinal nematode parasites in sheep

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