IgE Effector Mechanisms, in Concert with Mast Cells, Contribute to Acquired Host Defense against Staphylococcus aureus

Starkl, Philipp; Watzenboeck, Martin L.; Popov, Lauren M.; Zahalka, Sophie; Hladik, Anastasiya; Lakovits, Karin; Radhouani, Mariem; Haschemi, Arvand; Marichal, Thomas; Reber, Laurent L.; Gaudenzio, Nicolas; Sibilano, Riccardo; Stulik, Lukas; Fontaine, F.; Mueller, André; Amieva, Manuel R.; Galli, Stephen J.; Knapp, Sylvia

doi:10.1016/j.immuni.2020.11.012

Cited by 15 publications

(12 citation statements)

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“…The clearest evidence is the relationship between AD and FA: more than 80% of patients with FA have or have had AD ( 95 ). On the other hand, systemization of immune reactions initiated locally in the skin has been reported not only in FA but also in defense responses against S. aureus , proving that epicutaneous exposure to pathogenic bacteria ameliorates the symptomatology of secondary infections in the lung through an IgE- and mastocyte-mediated mechanism ( 96 ).…”

Section: Sphingolipids and Allergic Disordersmentioning

confidence: 99%

The Role of Sphingolipids in Allergic Disorders

et al. 2021

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Allergy is defined as a complex chronic inflammatory condition in which genetic and environmental factors are implicated. Sphingolipids are involved in multiple biological functions, from cell membrane components to critical signaling molecules. To date, sphingolipids have been studied in different human pathologies such as neurological disorders, cancer, autoimmunity, and infections. Sphingolipid metabolites, in particular, ceramide and sphingosine-1-phosphate (S1P), regulate a diverse range of cellular processes that are important in immunity and inflammation. Moreover, variations in the sphingolipid concentrations have been strongly associated with allergic diseases. This review will focus on the role of sphingolipids in the development of allergic sensitization and allergic inflammation through the activation of immune cells resident in tissues, as well as their role in barrier remodeling and anaphylaxis. The knowledge gained in this emerging field will help to develop new therapeutic options for allergic disorders.

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Section: Sphingolipids and Allergic Disordersmentioning

confidence: 99%

The Role of Sphingolipids in Allergic Disorders

et al. 2021

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“…Notably, a recent study has demonstrated a role for both MCs and IgE in the clearance of bacterial infection in the ear of mice. The importance of MCs in this study was linked to protection against secondary lung infection by Staphylococcus aureus ( 71 ) and there were indications that the MC proteases participated in the defense ( 71 ). MC proteases probably also contribute to bacterial clearance by cleavage of many bacterial virulence factors.…”

Section: In Vivo Targets For the MC Chymasesmentioning

confidence: 89%

Mast Cell and Basophil Granule Proteases - In Vivo Targets and Function

Hellman

Akula²,

Fu³

et al. 2022

Front. Immunol.

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Proteases are stored in very large amounts within abundant cytoplasmic granules of mast cells (MCs), and in lower amounts in basophils. These proteases are stored in their active form in complex with negatively charged proteoglycans, such as heparin and chondroitin sulfate, ready for rapid release upon MC and basophil activation. The absolute majority of these proteases belong to the large family of chymotrypsin related serine proteases. Three such enzymes are found in human MCs, a chymotryptic enzyme, the chymase, a tryptic enzyme, the tryptase and cathepsin G. Cathepsin G has in primates both chymase and tryptase activity. MCs also express a MC specific exopeptidase, carboxypeptidase A3 (CPA3). The targets and thereby the functions of these enzymes have for many years been the major question of the field. However, the fact that some of these enzymes have a relatively broad specificity has made it difficult to obtain reliable information about the biologically most important targets for these enzymes. Under optimal conditions they may cleave a relatively large number of potential targets. Three of these enzymes, the chymase, the tryptase and CPA3, have been shown to inactivate several venoms from snakes, scorpions, bees and Gila monster. The chymase has also been shown to cleave several connective tissue components and thereby to be an important player in connective tissue homeostasis. This enzyme can also generate angiotensin II (Ang II) by cleavage of Ang I and have thereby a role in blood pressure regulation. It also display anticoagulant activity by cleaving fibrinogen and thrombin. A regulatory function on excessive TH2 immunity has also been observed for both the chymase and the tryptase by cleavage of a highly selective set of cytokines and chemokines. The chymase also appear to have a protective role against ectoparasites such as ticks, mosquitos and leeches by the cleavage of their anticoagulant proteins. We here review the data that has accumulated concerning the potential in vivo functions of these enzymes and we discuss how this information sheds new light on the role of MCs and basophils in health and disease.

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“…It was recently discovered that the antibacterial activity of mast cells against Staphylococcus aureus (SA) in mice was markedly enhanced by the presence of IgE directed against bacterial components. Animal models deficient in IgE or FcϵRI were unable to mount protective immune responses against SA infections [ 38 ]. Furthermore, other authors have found that SIgED deficiency predisposes to recurrent upper and lower airways with common respiratory bacteria such as Haemophilus influenza, Moraxella catarrhalis , and Streptococcus pneumoniae [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Spectrum of Disease Manifestations in Patients with Selective Immunoglobulin E Deficiency

Picado

Landazuri

Vlagea

et al. 2021

JCM

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Background: Selective IgE deficiency (SIgED) has been previously evaluated in selected patients from allergy units. This study investigates the effects of SIgED on the entire population in a hospital setting and sought to delineate in detail the clinical aspects of SIgED. Methods: A retrospective study of the data obtained from electronic medical records of 52 adult patients (56% female) with a mean age of 43 years and IgE levels of <2.0 kU/L with normal immunoglobulin (Ig) IgG, IgA, and IgM levels, seen at our hospital, without selection bias, from 2010 to 2019. Results: Recurrent upper respiratory infections were recorded in 18 (34.6%) patients, pneumonia was recorded in 16 (30.7%) patients, bronchiectasis was recorded in 16 (30.7%) patients, and asthma was recorded in 10 (19.2%) patients. Eighteen patients (34.6%) suffered autoimmune clinical manifestations either isolated (19%) or combining two or more diseases (15%), Hashimoto’s thyroiditis being the most frequent (19%), which was followed by arthritis (10%) and thrombocytopenia and/or neutropenia (5.7%). Other less frequent associations were Graves’ disease, primary sclerosing cholangitis, Sjögren’s syndrome, and autoimmune hepatitis. Eczematous dermatitis (15.3%), chronic spontaneous urticaria (17.3%), and symptoms of enteropathy (21%) were also highly prevalent. Thirty percent of patients developed malignancies, with non-Hodgkin lymphomas (13.4%) being the most prevalent. Conclusions: The clinical manifestations of SIgED encompass a variety of infectious, non-infectious complications, and malignancy. Since it cannot be ruled out that some type of selection bias occurred in the routine assessment of IgE serum Ievels, prospective studies are required to better characterize SIgED and to determine whether it should be added to the list of antibody deficiencies.

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IgE Effector Mechanisms, in Concert with Mast Cells, Contribute to Acquired Host Defense against Staphylococcus aureus

Cited by 15 publications

References 0 publications

The Role of Sphingolipids in Allergic Disorders

The Role of Sphingolipids in Allergic Disorders

Mast Cell and Basophil Granule Proteases - In Vivo Targets and Function

Spectrum of Disease Manifestations in Patients with Selective Immunoglobulin E Deficiency

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