Mast cells: new therapeutic target in helminth immune modulation

Vukman, Krisztina V.; Lalor, Richard; Aldridge, Allison; O’Neill, Sandra M.

doi:10.1111/pim.12295

Cited by 20 publications

(19 citation statements)

References 102 publications

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“…Host defenses against helminth infections are mediated by activation of T H 2 cells, group 2 innate lymphoid cells, eosinophils, and MCs in line with increased levels of cytokines, such as IL-4, IL-5, and IL-13. [83][84][85][86] MCs have been reported to exert direct cytotoxic effects on helminths through secretion of serine proteases (chymase and tryptase). 42,85,87 Furthermore, MCP-1 has been shown to increase intestinal epithelial barrier permeability, resulting in increased luminal flow and thereby parasite expulsion.…”

Section: Multifaceted Roles Of Mcs In Host Defense Against Infectionmentioning

confidence: 99%

Mast cells as protectors of health

Dudeck

Köberle

Goldmann

et al. 2019

Journal of Allergy and Clinical Immunology

108

106

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Mast cells (MCs), which are well known for their effector functions in T H 2-skewed allergic and also autoimmune inflammation, have become increasingly acknowledged for their role in protection of health. It is now clear that they are also key modulators of immune responses at interface organs, such as the skin or gut. MCs can prime tissues for adequate inflammatory responses and cooperate with dendritic cells in T-cell activation. They also regulate harmful immune responses in trauma and help to successfully orchestrate pregnancy. This review focuses on the beneficial effects of MCs on tissue homeostasis and elimination of toxins or venoms. MCs can enhance pathogen clearance in many bacterial, viral, and parasitic infections, such as through Toll-like receptor 2-triggered degranulation, secretion of antimicrobial cathelicidins, neutrophil recruitment, or provision of extracellular DNA traps. The role of MCs in tumors is more ambiguous; however, encouraging new findings show they can change the tumor microenvironment toward antitumor immunity when adequately triggered. Uterine tissue remodeling by a-chymase (mast cell protease [MCP] 5) is crucial for successful embryo implantation. MCP-4 and the tryptase MCP-6 emerge to be protective in central nervous system trauma by reducing inflammatory damage and excessive scar formation, thereby protecting axon growth. Last but not least, proteases, such as carboxypeptidase A, released by FcεRIactivated MCs detoxify an increasing number of venoms and endogenous toxins. A better understanding of the plasticity of MCs will help improve these advantageous effects and hint at ways to cut down detrimental MC actions.

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Section: Multifaceted Roles Of Mcs In Host Defense Against Infectionmentioning

confidence: 99%

Mast cells as protectors of health

Dudeck

Köberle

Goldmann

et al. 2019

Journal of Allergy and Clinical Immunology

108

106

View full text Add to dashboard Cite

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“…However, leukotrienes, particularly, LTB 4 , can reduce S. venezuelensis worm burden, possibly via the recruitment of certain inflammatory cells [64]. Furthermore, MCs have the potential to shape parasite-associated adaptive immune responses via production of soluble mediators or via cell-cell interactions with DCs and other antigen-presenting cells [4, 44, 65]. Finally, IgE- independent MC degranulation has been shown to enhance early phases of Th2 immune responses following infections with Heligmosomoides polygyrus and Trichuris muris [44, 66].…”

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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“…1,2 The mobilization of mucosal immunity in the context of enteric helminth infection is multi-faceted, complex and intriguing but a comprehensive discussion of such is beyond the scope of this commentary: the reader is referred to excellent recent reviews of this topic. [3][4][5][6][7][8] For the purposes of this review we will use 'epithelial permeability' to denote studies that address the physical properties of the epithelial layer and 'barrier function' is used as a more encompassing term that refers to the many extrinsic (e.g. mucus, IgA, commensal microbiota) components of the intestinal barrier.…”

Section: Introductionmentioning

confidence: 99%

Helminths and intestinal barrier function

2017

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Approximately one-sixth of the worlds' population is infected with helminths and this class of parasite takes a major toll on domestic livestock. The majority of species of parasitic helminth that infect mammals live in the gut (the only niche for tapeworms) where they contact the hosts' epithelial cells. Here, the helminth-intestinal epithelial interface is reviewed in terms of the impact on, and regulation of epithelial barrier function, both intrinsic (epithelial permeability) and extrinsic (mucin, bacterial peptides, commensal bacteria) elements of the barrier. The data available on direct effects of helminths on epithelial permeability are scant, fragmentary and pales in comparison with knowledge of mobilization of immune reactions and effector cells in response to helminth parasites and how these impact intestinal barrier function. The interaction of helminth-host and helminthhost-bacteria is an important determinant of gut form and function and precisely defining these interactions will radically alter our understanding of normal gut physiology and pathophysiological reactions, revealing new approaches to infection with parasitic helminths, bacterial pathogens and idiopathic auto-inflammatory disease.

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Mast cells: new therapeutic target in helminth immune modulation

Cited by 20 publications

References 102 publications

Mast cells as protectors of health

Mast cells as protectors of health

IgE and mast cells in host defense against parasites and venoms

Helminths and intestinal barrier function

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