Mast Cell Functions Linking Innate Sensing to Adaptive Immunity

Katsoulis‐Dimitriou, Konstantinos; Kotrba, Johanna; Voß, Martin; Dudeck, Jan; Dudeck, Anne

doi:10.3390/cells9122538

Cited by 40 publications

(44 citation statements)

References 152 publications

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“…As components of innate immunity as well as bridges between innate and adaptive immune functions, MCs are ideally localized in tissues to act as sentinels that organize antimicrobial and anti-parasitic defenses [ 74 , 75 ]. On the other hand, MCs can also trigger hypersensitivity reactions upon exposure to exogenous antigens, drugs, venoms, or endogenous alarmins released by damaged or inflamed tissues.…”

Section: Discussionmentioning

confidence: 99%

Cytokines Stimulated by IL-33 in Human Skin Mast Cells: Involvement of NF-κB and p38 at Distinct Levels and Potent Co-Operation with FcεRI and MRGPRX2

Franke

Wang

Zuberbier

et al. 2021

IJMS

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The IL-1 family cytokine IL-33 activates and re-shapes mast cells (MCs), but whether and by what mechanisms it elicits cytokines in MCs from human skin remains poorly understood. The current study found that IL-33 activates CCL1, CCL2, IL-5, IL-8, IL-13, and TNF-α, while IL-1β, IL-6, IL-31, and VEGFA remain unaffected in cutaneous MCs, highlighting that each MC subset responds to IL-33 with a unique cytokine profile. Mechanistically, IL-33 induced the rapid (1–2 min) and durable (2 h) phosphorylation of p38, whereas the phosphorylation of JNK was weaker and more transient. Moreover, the NF-κB pathway was potently activated, as revealed by IκB degradation, increased nuclear abundance of p50/p65, and vigorous phosphorylation of p65. The activation of NF-κB occurred independently of p38 or JNK. The induced transcription of the cytokines selected for further study (CCL1, CCL2, IL-8, TNF-α) was abolished by interference with NF-κB, while p38/JNK had only some cytokine-selective effects. Surprisingly, at the level of the secreted protein products, p38 was nearly as effective as NF-κB for all entities, suggesting post-transcriptional involvement. IL-33 did not only instruct skin MCs to produce selected cytokines, but it also efficiently co-operated with the allergic and pseudo-allergic/neurogenic activation networks in the production of IL-8, TNF-α, CCL1, and CCL2. Synergism was more pronounced at the protein than at the mRNA level and appeared stronger for MRGPRX2 ligands than for FcεRI. Our results underscore the pro-inflammatory nature of an acute IL-33 stimulus and imply that especially in combination with allergens or MRGPRX2 agonists, IL-33 will efficiently amplify skin inflammation and thereby aggravate inflammatory dermatoses.

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Section: Discussionmentioning

confidence: 99%

Cytokines Stimulated by IL-33 in Human Skin Mast Cells: Involvement of NF-κB and p38 at Distinct Levels and Potent Co-Operation with FcεRI and MRGPRX2

Franke

Wang

Zuberbier

et al. 2021

IJMS

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“…MCs are mainly known for their key effector functions in type I allergy, where they are activated by crosslinking of cell-surface-bound FcεRI–IgE complexes by specific antigen [ 80 , 81 , 82 ]. Additionally, MCs are known to exhibit important innate and adaptive immunity functions, as we previously discussed [ 83 ]. Given their response repertoire, consisting of a wide range of surface receptors and proinflammatory mediators, and their strategic positioning, MCs contribute to the first line of host defense against invading pathogens [ 80 , 82 , 84 , 85 , 86 ].…”

Section: Role Of Mast Cells In Barrier Integrity and Host Defensementioning

confidence: 99%

“…Collectively, as discussed in more detail in Katsoulis-Dimitriou et al [ 83 ], MCs critically contribute to innate host defense but also link the innate and adaptive immune response.…”

Section: Role Of Mast Cells In Barrier Integrity and Host Defensementioning

confidence: 99%

Mast Cells in the Skin: Defenders of Integrity or Offenders in Inflammation?

Voß

Kotrba

Gaffal

et al. 2021

IJMS

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Mast cells (MCs) are best-known as key effector cells of immediate-type allergic reactions that may even culminate in life-threatening anaphylactic shock syndromes. However, strategically positioned at the host–environment interfaces and equipped with a plethora of receptors, MCs also play an important role in the first-line defense against pathogens. Their main characteristic, the huge amount of preformed proinflammatory mediators embedded in secretory granules, allows for a rapid response and initiation of further immune effector cell recruitment. The same mechanism, however, may account for detrimental overshooting responses. MCs are not only detrimental in MC-driven diseases but also responsible for disease exacerbation in other inflammatory disorders. Focusing on the skin as the largest immune organ, we herein review both beneficial and detrimental functions of skin MCs, from skin barrier integrity via host defense mechanisms to MC-driven inflammatory skin disorders. Moreover, we emphasize the importance of IgE-independent pathways of MC activation and their role in sustained chronic skin inflammation and disease exacerbation.

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“…These findings would support the role of MCs in uptaking and eliminating Mtb through phagocytosis or serve as a reservoir of intracellular Mtb during the active phase of TB infection. Although is not within the scope of this study, further research is needed to investigate whether MCs contribute to T cell activation as described in other conditions 36 , 38 , 39 via Mtb -antigen presentation.…”

Section: Discussionmentioning

confidence: 98%

Differential mast cell numbers and characteristics in human tuberculosis pulmonary lesions

Garcia-Rodriguez

Bini

Gamboa‐Domínguez

et al. 2021

Sci Rep

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Tuberculosis (TB) is still a major worldwide health threat and primarily a lung disease. The innate immune response against Mycobacterium tuberculosis (Mtb) is orchestrated by dendritic cells, macrophages, neutrophils, natural killer cells and apparently mast cells (MCs). MCs are located at mucosal sites including the lungs and contribute in host-defence against pathogens, but little is known about their role during Mtb infection. This study investigates the location and characteristics of MCs in TB lesions to assess their contribution to TB pathology. To this purpose, number, location and phenotype of MCs was studied in 11 necropsies of pulmonary TB and 3 necropsies of non-TB infected lungs that were used as controls. MCs were localised at pneumonic areas, in the granuloma periphery and particularly abundant in fibrotic tissue. Furthermore, MCs displayed intracellular Mtb and IL-17A and TGF-β immunostaining. These findings were validated by analysing, post-mortem lung tissue microarrays from 44 individuals with pulmonary TB and 25 control subjects. In affected lungs, increased numbers of MCs expressing intracellularly both tryptase and chymase were found at fibrotic sites. Altogether, our data suggest that MCs are recruited at the inflammatory site and that actively produce immune mediators such as proteases and TGF-β that may be contributing to late fibrosis in TB lesions.

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Mast Cell Functions Linking Innate Sensing to Adaptive Immunity

Cited by 40 publications

References 152 publications

Cytokines Stimulated by IL-33 in Human Skin Mast Cells: Involvement of NF-κB and p38 at Distinct Levels and Potent Co-Operation with FcεRI and MRGPRX2

Cytokines Stimulated by IL-33 in Human Skin Mast Cells: Involvement of NF-κB and p38 at Distinct Levels and Potent Co-Operation with FcεRI and MRGPRX2

Mast Cells in the Skin: Defenders of Integrity or Offenders in Inflammation?

Differential mast cell numbers and characteristics in human tuberculosis pulmonary lesions

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