Elevated Toll-Like Receptor-Induced CXCL8 Secretion in Human Blood Basophils from Allergic Donors Is Independent of Toll-Like Receptor Expression Levels

Steiner, Markus J.; Hawranek, Thomas; Schneider, M; Ferreira, Fátima; Horejs‐Hoeck, Jutta; Harrer, Andrea; Himly, Martin

doi:10.1371/journal.pone.0149275

Cited by 5 publications

(5 citation statements)

References 20 publications

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“…We also confirmed that IgE cross-linking induced IL-8 production in equine basophils and IgE-binding monocytes, supporting an FceRI-mediated activation pathway in both cell types. IL-8 production by basophils and IgE-binding monocytes has previously been reported in human studies (57,16,17,19,20) and further supports the use of the well-controlled horse model as a comparative approach for studying IL-8 in the context of IgE-mediated allergy.…”

Section: Discussionsupporting

confidence: 76%

“…To the best of our knowledge, this is the first study to compare IL-8 production between allergic and healthy individuals after IgE stimulation by basophils and IgE-binding monocytes. IL-8 1 basophils have been compared in allergic humans but only after TLR stimulation (16). In this article, we show that allergic individuals have increased percentages of peripheral IL-8 1 IgE-binding monocytes compared with healthy controls upon IgE cross-linking.…”

Section: Discussionmentioning

confidence: 84%

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IgE-Binding Monocytes Have an Enhanced Ability to Produce IL-8 (CXCL8) in Animals with Naturally Occurring Allergy

Larson

Babasyan

Wagner

2021

The Journal of Immunology

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IL-8 is a potent chemokine that recruits neutrophils and basophils to promote inflammation in many species. IL-8 is produced by many cell types, including monocytes. In this study, we report a novel role for IgE-binding monocytes, a rare peripheral immune cell type, to promote allergic inflammation through IL-8 production in a horse model of natural IgE-mediated allergy. We developed a mAb with confirmed specificity for both recombinant and native equine IL-8 for flow cytometric analysis. Equine IL-8 was produced by CD14+/MHC class II+/CD16− monocytes, including a subpopulation of IgE-binding monocytes, following stimulation with LPS. In addition, IgE cross-linking induced IL-8 production by both peripheral blood basophils and IgE-binding monocytes. IL-8 production was compared between healthy horses and those with a naturally occurring IgE-mediated skin allergy, Culicoides hypersensitivity. Allergic horses had significantly higher percentages of IL-8+ IgE-binding monocytes after IgE cross-linking. In contrast, frequencies of IL-8+ basophils after IgE cross-linking were similar in all horses, regardless of allergic disease, highlighting IgE-binding monocytes as a novel source of IL-8 during allergy. We concluded that IgE-binding monocytes from allergic individuals have an increased capacity for IL-8 production and likely contribute to the recruitment of innate immune cells during IgE-mediated allergy and promotion of inflammation during repeated allergen contact.

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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 84%

IgE-Binding Monocytes Have an Enhanced Ability to Produce IL-8 (CXCL8) in Animals with Naturally Occurring Allergy

Larson

Babasyan

Wagner

2021

The Journal of Immunology

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“…We, therefore, recommend inclusion of plots/histograms in the publications to allow the reader evaluating the basophil activation profile. To circumvent bystander effects caused by interaction with other cells basophil purification protocols, as described recently (Steiner et al, 2016 ), may be considered, in particular when investigating more specific questions beyond diagnosis. Overall, the basophil response in BAT is influenced by many so far unpredictable factors which may impair the quality of results in certain cases (Chirumbolo, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Basophil Reactivity as Biomarker in Immediate Drug Hypersensitivity Reactions—Potential and Limitations

2016

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Immediate drug hypersensitivity reactions (DHRs) resemble typical immunoglobulin E (IgE)-mediated symptoms. Clinical manifestations range from local skin reactions, gastrointestinal and/or respiratory symptoms to severe systemic involvement with potential fatal outcome. Depending on the substance group of the eliciting drug the correct diagnosis is a major challenge. Skin testing and in vitro diagnostics are often unreliable and not reproducible. The involvement of drug-specific IgE is questionable in many cases. The culprit substance (parent drug or metabolite) and potential cross-reacting compounds are difficult to identify, patient history and drug provocation testing often remain the only means for diagnosis. Hence, several groups proposed basophil activation test (BAT) for the diagnosis of immediate DHRs as basophils are well-known effector cells in allergic reactions. However, the usefulness of BAT in immediate DHRs is highly variable and dependent on the drug itself plus its capacity to spontaneously conjugate to serum proteins. Stimulation with pure solutions of the parent drug or metabolites thereof vs. drug-protein conjugates may influence sensitivity and specificity of the test. We thus, reviewed the available literature about the use of BAT for diagnosing immediate DHRs against drug classes such as antibiotics, radio contrast media, neuromuscular blocking agents, non-steroidal anti-inflammatory drugs, and biologicals. Influencing factors like the selection of stimulants or of the identification and activation markers, the stimulation protocol, gating strategies, and cutoff definition are addressed in this overview on BAT performance. The overall aim is to evaluate the suitability of BAT as biomarker for the diagnosis of immediate drug-induced hypersensitivity reactions.

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“…Simultaneous stimulation of the high affinity IgE receptor and TLR4 or TLR9 synergistically upregulated IL-4, CXCL8, IL-13, and CCL5 secretion [124]. Moreover, an elevated CXCL8 secretion was observed in allergic individuals upon TLR1/2 and TLR2/6 stimulation [122]. These findings suggest a connection between the pathogen-induced basophil activation and an allergic response of basophils.…”

Section: The Basophil In the Immune Networkmentioning

confidence: 99%

The Evolution of Human Basophil Biology from Neglect towards Understanding of Their Immune Functions

Steiner

Huber

Harrer

et al. 2016

BioMed Research International

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Being discovered long ago basophils have been neglected for more than a century. During the past decade evidence emerged that basophils share features of innate and adaptive immunity. Nowadays, basophils are best known for their striking effector role in the allergic reaction. They hence have been used for establishing new diagnostic tests and therapeutic approaches and for characterizing natural and recombinant allergens as well as hypoallergens, which display lower or diminished IgE-binding activity. However, it was a long way from discovery in 1879 until identification of their function in hypersensitivity reactions, including adverse drug reactions. Starting with a historical background, this review highlights the modern view on basophil biology.

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Elevated Toll-Like Receptor-Induced CXCL8 Secretion in Human Blood Basophils from Allergic Donors Is Independent of Toll-Like Receptor Expression Levels

Cited by 5 publications

References 20 publications

IgE-Binding Monocytes Have an Enhanced Ability to Produce IL-8 (CXCL8) in Animals with Naturally Occurring Allergy

IgE-Binding Monocytes Have an Enhanced Ability to Produce IL-8 (CXCL8) in Animals with Naturally Occurring Allergy

Basophil Reactivity as Biomarker in Immediate Drug Hypersensitivity Reactions—Potential and Limitations

The Evolution of Human Basophil Biology from Neglect towards Understanding of Their Immune Functions

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