Innate Immunity Induces the Accumulation of Lung Mast Cells During Influenza Infection

Zarnegar, Behdad; Westin, Annika; Evangelidou, Syrmoula; Hallgren, Jenny

doi:10.3389/fimmu.2018.02288

Cited by 11 publications

(9 citation statements)

References 39 publications

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“…When the controls were subgrouped according to their self‐reported health issues, two of the four control subjects with the highest MCp frequency reported respiratory problems (none of the controls were treated with inhaled corticosteroids). We recently found that during acute influenza infection in mice, innate immunity triggers the recruitment of MCp to the lung to a similar extent as allergic inflammation . The individuals included in our study had to be free from cold symptoms 2 weeks prior to the clinic visit.…”

Section: Discussionmentioning

confidence: 99%

Circulating mast cell progenitors correlate with reduced lung function in allergic asthma

Salomonsson

Malinovschi

Kalm-Stephens

et al. 2019

Clin Experimental Allergy

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This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. SummaryBackground: Studies using mouse models have revealed that mast cell progenitors are recruited from the blood circulation to the lung during acute allergic airway inflammation. The discovery of a corresponding human mast cell progenitor population in the blood has enabled to study the relation of circulating mast cell progenitors in clinical settings. Objectives:To explore the possible association between the frequency of mast cell progenitors in the blood circulation and allergic asthma, we assessed the relation of this recently identified cell population with asthma outcomes and inflammatory mediators in allergic asthmatic patients and controls.Methods: Blood samples were obtained, and spirometry was performed on 38 wellcontrolled allergic asthmatic patients and 29 controls. The frequency of blood mast cell progenitors, total serum IgE and 180 inflammation-and immune-related plasma proteins were quantified.Results: Allergic asthmatic patients and controls had a similar mean frequency of blood mast cell progenitors, but the frequency was higher in allergic asthmatic patients with reduced FEV 1 and PEF (% of predicted) as well as in women. The level of fibroblast growth factor 21 (FGF-21) correlated positively with the frequency of mast cell progenitors, independent of age and gender, and negatively with lung function.The expression of FcεRI on mast cell progenitors was higher in allergic asthmatic patients and correlated positively with the level of total IgE in the controls but not in the asthmatic patients. Conclusion: Elevated levels of circulating mast cell progenitors are related to reduced lung function, female gender and high levels of FGF-21 in young adults with allergic asthma. K E Y W O R D S allergic asthma, asthma, lung function, mast cell progenitors, mast cells | 875 SALOMONSSON et AL. S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section at the end of the article. How to cite this article: Salomonsson M, Malinovschi A, Kalm-Stephens P, et al. Circulating mast cell progenitors correlate with reduced lung function in allergic asthma. Clin

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Section: Discussionmentioning

confidence: 99%

Circulating mast cell progenitors correlate with reduced lung function in allergic asthma

Salomonsson

Malinovschi

Kalm-Stephens

et al. 2019

Clin Experimental Allergy

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“…In parallel, we demonstrated that influenza infection in mice induced the recruitment of MCps to the lung, which later gave rise to mast cells with intermediate expression of integrin β7 (immature/induced) and even later increased the number of mature mast cells with low expression of integrin β7 (38). While the recruitment of MCps induced by allergic lung inflammation was dependent on an adaptive immune response (54, 55), the influenza-induced MCp recruitment to the lung was due to the induction of innate immune responses (60). As respiratory infections commonly cause exacerbations of asthma symptoms, we think it is intriguing that influenza infections induces mast cell accumulation in the mouse lung.…”

Section: Mast Cell Accumulation In the Lung And The Mechanisms Behindmentioning

confidence: 99%

“…In vivo , TLR4-mediated mast cell activation was demonstrated to enhance eosinophilia and cytokine release in an OVA-model of allergic airway inflammation using mast cell-deficient (Kit W / Wv ) mice and reconstitution experiments (127). Furthermore, intranasal administrations of poly I:C expand the number of lung MCps in a TLR3-dependent fashion (60). To summarize, the activation of pattern recognition receptors may directly or indirectly induce or modulate mast cell responses in the allergic lung.…”

Section: Ige-independent Activation Of Mast Cells In Asthmamentioning

confidence: 99%

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Mast Cells and Their Progenitors in Allergic Asthma

2019

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Mast cells and their mediators have been implicated in the pathogenesis of asthma and allergy for decades. Allergic asthma is a complex chronic lung disease in which several different immune cells, genetic factors and environmental exposures influence the pathology. Mast cells are key players in the asthmatic response through secretion of a multitude of mediators with pro-inflammatory and airway-constrictive effects. Well-known mast cell mediators, such as histamine and bioactive lipids are responsible for many of the physiological effects observed in the acute phase of allergic reactions. The accumulation of mast cells at particular sites of the allergic lung is likely relevant to the asthma phenotype, severity and progression. Mast cells located in different compartments in the lung and airways have different characteristics and express different mediators. According to in vivo experiments in mice, lung mast cells develop from mast cell progenitors induced by inflammatory stimuli to migrate to the airways. Human mast cell progenitors have been identified in the blood circulation. A high frequency of circulating human mast cell progenitors may reflect ongoing pathological changes in the allergic lung. In allergic asthma, mast cells become activated mainly via IgE-mediated crosslinking of the high affinity receptor for IgE (FcεRI) with allergens. However, mast cells can also be activated by numerous other stimuli e.g. toll-like receptors and MAS-related G protein-coupled receptor X2. In this review, we summarize research with implications on the role and development of mast cells and their progenitors in allergic asthma and cover selected activation pathways and mast cell mediators that have been implicated in the pathogenesis. The review places an emphasis on describing mechanisms identified using in vivo mouse models and data obtained by analysis of clinical samples.

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“…Importantly, poly(I:C)-activated upregulation of TLR3 expression was also demonstrated in murine bone marrowderived cultured MCs (BMMCs), though only at the mRNA level [31]. Furthermore, poly(I:C) stimulated a six-fold increase in the total number of lung MCs via TLR3 [49].…”

Section: Discussionmentioning

confidence: 96%

The Response of Tissue Mast Cells to TLR3 Ligand Poly(I:C) Treatment

Witczak

Brzezińska‐Błaszczyk

Agier

2020

Journal of Immunology Research

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Mast cells (MCs) are found mainly at the anatomical sites exposed to the external environment; thus, they are localized close to blood vessels, lymphatic vessels, and a multitude of immune cells. Moreover, those cells can recognize invading pathogens through a range of surface molecules known as pathogen recognition receptors (PRRs), mainly Toll-like receptors (TLRs). MCs are extensively engaged in the control and clearance of bacterial infections, but much less is known about their contribution to antiviral host response as well as pathomechanisms of virus-induced diseases. In the study, we employed in vivo differentiated mature tissue mast cells freshly isolated from rat peritoneal cavity. Here, we demonstrated that rat peritoneal mast cells (rPMCs) express viral dsRNA-specific TLR3 molecule (intracellularly and on the cell surface) as well as other proteins associated with cellular antiviral response: IRF3, type I and II IFN receptors, and MHC I. We found that exposure of rPMCs to viral dsRNA mimic, i.e., poly(I:C), induced transient upregulation of surface TLR3 (while temporarily decreased TLR3 intracellular expression), type II IFN receptor, and MHC I. TLR3 ligand-stimulated rPMCs did not degranulate but generated and/or released type I IFNs (IFN-α and IFNβ) as well as proinflammatory lipid mediators (cysLTs), cytokines (TNF, IL-1β), and chemokines (CCL3, CXCL8). We documented that rPMC priming with poly(I:C) did not affect FcεRI-dependent degranulation. However, their costimulation with TLR3 agonist and anti-IgE led to a significant increase in cysLT and TNF secretion. Our findings confirm that MCs may serve as active participants in the antiviral immune response. Presented data on modulated FcεRI-mediated MC secretion of mediators upon poly(I:C) treatment suggests that dsRNA-type virus infection could influence the severity of allergic reactions.

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Innate Immunity Induces the Accumulation of Lung Mast Cells During Influenza Infection

Cited by 11 publications

References 39 publications

Circulating mast cell progenitors correlate with reduced lung function in allergic asthma

Circulating mast cell progenitors correlate with reduced lung function in allergic asthma

Mast Cells and Their Progenitors in Allergic Asthma

The Response of Tissue Mast Cells to TLR3 Ligand Poly(I:C) Treatment

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