Neutrophil trapping and nexocytosis are mast cell processes for inflammatory signal relay
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1000478 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25473302_1.fastq.gz | Fastqsanger.gz | |||
| SRR25473302_2.fastq.gz | Fastqsanger.gz | |||
| SRR25473303_1.fastq.gz | Fastqsanger.gz | |||
| SRR25473303_2.fastq.gz | Fastqsanger.gz | |||
| SRR25473304_1.fastq.gz | Fastqsanger.gz |
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Project description:Neutrophils are sentinel immune cells with essential roles for our anti-microbial defense. Most of our knowledge on neutrophil trafficking and tissue navigation derived from models of sterile inflammation and infection. Here, we analyzed allergen-challenged mouse tissues and discovered that degranulating mast cells (MCs) trap living neutrophils inside them. MCs release the attractant leukotriene B4 to re-route neutrophils toward them, thus exploiting a chemotactic system which neutrophils normally use for intercellular communication. Neutrophils die as a consequence of mast cell intracellular trap (MIT) formation, but their undigested material remains stored inside MC vacuoles over days. MCs can use this debris to increase their functional and metabolic fitness. Additionally, they can also exocytose active neutrophilic compounds with a time delay (nexocytosis) and elicit a pro-inflammatory type 1 interferon response in surrounding macrophages. Together, our study highlights neutrophil trapping and nexocytosis as mast cell-dependent processes, which may relay neutrophilic features over the course of chronic allergic inflammation.
2024-06-07 | GSE239647 | GEO
Project description:Degranulating mast cells (MCs) release inflammatory mediators (proteins, lipids, small molecules), including chemokines and chemoattractants, which recruit other immune cells in tissues. Neutrophils can initiate self-amplifying swarming responses via intercellular communication through the lipid leukotriene B4 (LTB4). Initially discovered by two-photon intravital microscopy in mice and confocal live cell imaging, we show that degranulating MCs release LTB4 and exploit this attractant by re-directing neutrophils to MCs. In a process generally termed entosis, neutrophil cluster formation around MCs results in the trapping of living neutrophils inside MC vacuoles in vivo and in vitro. Thus, we identify a novel cell-in-cell structure between MCs and neutrophils, which we term “Mast Cell Intracellular Trap” (MIT). Compared to MCs, MITs revealed improved MC metabolism and recovery after degranulation. This leads to several benefits for MITs: (1) they can be more efficiently re-stimulated than MCs, (2) they show improved survival under nutrient limitation, and (3) MITs store neutrophil proteins, DNA and effector molecules, which can be released after re-stimulation. In this context, we compare the secretome (secreted proteins) of MCs and MITs (in cell culture) before and subsequent to degranulation via label-free nanoLC-MS. In summary, mast cells trap and cannibalize swarming neutrophils, which supply nutrients, proteins and inflammatory molecules to recovering MCs. Our studies may have potential implications for chronically activated MCs in MC-related immune disorders.
2024-06-18 | PXD044140 | Pride
Project description:It is not understood, how mechanical signals influence the behavior and action of circulating cells in our body. Previous studies showed that the process of migration through narrow slits might enhance lifespan of polymorpho-nuclear cells (PMN / neutrophil). But it is unknown, how the mechanical signal is received, relayed, and translated into specific phenotype shift in PMN. Here we investigated whether compressional force affects defense system of circulating lymphocytes by increasing their killing ability during migration through narrow endothelial junctions. To decipher the receiving and transducing components of this mechanical signal relay process, we performed gene expression analysis between transmigrated and non-transmigrated neutrophils. Comparison of early gene-expression pattern of transmigrated and non-transmigrated neutrophils revealed a huge change in gene expression profile. Molecular and genetic analysis of the proteins revealed from gene-expression analysis led us to understand the mechanism of mechanical signal relay from the neutrophil membrane to bacterial-killing machinery. As neutrophils are most abundant and immediate-responding circulating immune cells in our body, our study advances the path for understanding the general process of mechano-transduction, and mechano-modulatory applications with mechanically enhanced neutrophils.
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Project description:Citrullination is an important post-translational modification implicated in many diseases including rheumatoid arthritis (RA), Alzheimer's disease and cancer. Neutrophil and mast cells have different protein-arginine deiminases expression profile and ionomycin induced activation make them the ideal cellular models to study proteins susceptible to citrullination. We performed high resolution mass spectrometry and stringent data filtration to identify citrullination sites in neutrophil and mast cells treated with and without ionomycin. We identified a total of 831 validated citrullination sites on 393 proteins. Several of these citrullinated proteins are important component of pathways involved in innate immune responses. Using this benchmark primary sequence dataset, we developed machine learning models to predict citrullination in neutrophil and mast cells proteins. Our neutrophil protein citrullination prediction model achieved greater than 76% accuracy and 0.39 Matthews correlation coefficient (MCC) on an independent validation set. In summary, this study provides the largest number of validated citrullination sites in neutrophil and mast cell proteins. The use of our novel motif analysis approach to predict citrullination sites will facilitate the discovery of novel protein substrates of protein-arginine deiminases (PADs), which may be key to understanding immunopathologies of various diseases.
2022-01-12 | PXD023131 | Pride
Project description:Neutrophil recruitment to inflammation sites purportedly depends on sequential waves of chemoattractants. Current models propose that leukotriene B(4) (LTB(4)), a secondary chemoattractant secreted by neutrophils in response to primary chemoattractants such as formyl peptides, is important in initiating the inflammation process. In this study we demonstrate that LTB(4) plays a central role in neutrophil activation and migration to formyl peptides. We show that LTB(4) production dramatically amplifies formyl peptide-mediated neutrophil polarization and chemotaxis by regulating specific signaling pathways acting upstream of actin polymerization and MyoII phosphorylation. Importantly, by analyzing the migration of neutrophils isolated from wild-type mice and mice lacking the formyl peptide receptor 1, we demonstrate that LTB(4) acts as a signal to relay information from cell to cell over long distances. Together, our findings imply that LTB(4) is a signal-relay molecule that exquisitely regulates neutrophil chemotaxis to formyl peptides, which are produced at the core of inflammation sites.
| S-EPMC4141281 | biostudies-literature
Project description:Neutrophils are activated and attracted to sites of anaphylaxis by degranulating tissue resident mast cells. After they facilitate inflammation and an anti-microbial immune response. However, the dynamics of neutrophils and direct interactions with mast cells are poorly investigated yet. By approaching 2-photon intravital microscopy and live cell imaging, we show that degranulating mast cells induce neutrophil swarming by releasing leukotriene B4 (LTB4). Attracted neutrophils interact with mast cells and surprisingly penetrate inside mast cells where they are stably trapped inside mast cell granules. We call this novel form of cell-in-cell structure “Mast Cell Intracellular Trap” (MIT). Trapped neutrophils and mast cells are both viable in the first 12 hours after MIT formation. However, neutrophils start to dye after 12hrs and translatome analysis of mast cells revealed improved mast cell metabolism and recovery. Therefore, neutrophils allow a faster and more efficient mast cell re-stimulation. Furthermore, mast cells get more resistant to extracellular nutrient limitations. Thus, beside their inflammatory role in anaphylaxis, neutrophils support mast cell recovery by forming a cell in cell structure. This might affect chronic inflammation and recurrent infections.
2024-06-07 | GSE168801 | GEO
Project description:The meninges are generally considered relatively inert tissues that house the CSF and provide protection for the brain and spinal cord. However, our previous studies using Kit mutant (Kit W/Wv) mast cell-deficient mice demonstrated that mast cells residing in the dura mater and pia mater exacerbate the severity of experimental autoimmune encephalomyelitis (EAE), the rodent model of the CNS demyelinating disease, multiple sclerosis. These data suggest that the meninges are sites of active immune responses in disease. Gene expression profiles of meningeal tissue from wild type and mast cell deficient mice prior to and at day 6 post-EAE induction were found highly distinct. Increases in both mast cell- and neutrophil-associated transcripts were among the notable disease-related changes observed in wild type mice. Kinetic analyses show that meningeal mast cells are activated within 24 hours of disease induction to express multiple mediators including IL-1b and TNF as well as the neutrophil chemoattractant, CXCL2, an observation corresponding with an influx of neutrophils to the meninges. Neutrophil recruitment as well as the disease-related loss of BBB integrity is dependent on mast cell-derived TNF. These data provide unequivocal evidence that the meninges are sites of early inflammatory events in EAE. Mast cells residing within these tissues promote disease by orchestrating an early and efficient immune cell co-localization resulting in a robust local inflammatory response and a breach of the proximal BBB. We hypothesize that these events reflect an aberrant manifestation of the normal immune surveillance role of the meninges in infection settings.
2013-01-01 | GSE37191 | GEO
Project description:The meninges are generally considered relatively inert tissues that house the CSF and provide protection for the brain and spinal cord. However, our previous studies using Kit mutant (Kit W/Wv) mast cell-deficient mice demonstrated that mast cells residing in the dura mater and pia mater exacerbate the severity of experimental autoimmune encephalomyelitis (EAE), the rodent model of the CNS demyelinating disease, multiple sclerosis. These data suggest that the meninges are sites of active immune responses in disease. Gene expression profiles of meningeal tissue from wild type and mast cell deficient mice prior to and at day 6 post-EAE induction were found highly distinct. Increases in both mast cell- and neutrophil-associated transcripts were among the notable disease-related changes observed in wild type mice. Kinetic analyses show that meningeal mast cells are activated within 24 hours of disease induction to express multiple mediators including IL-1b and TNF as well as the neutrophil chemoattractant, CXCL2, an observation corresponding with an influx of neutrophils to the meninges. Neutrophil recruitment as well as the disease-related loss of BBB integrity is dependent on mast cell-derived TNF. These data provide unequivocal evidence that the meninges are sites of early inflammatory events in EAE. Mast cells residing within these tissues promote disease by orchestrating an early and efficient immune cell co-localization resulting in a robust local inflammatory response and a breach of the proximal BBB. We hypothesize that these events reflect an aberrant manifestation of the normal immune surveillance role of the meninges in infection settings. Immunized WT and Kit W/Wv mice were sacrificed on Day 6 post-immunization and perfused with PBS as were naïve littermate control mice. The dura mater was immediately removed from the calvarium of the skull and pooled (10 mice/group, 4 groups). RNA was isolated using SV Total RNA Isolation System (Promega). Each pool was analyzed in technical triplicates. Briefly, cRNA was synthesized and amplified/labeled using the Affymetrix Express Kit, then fragmented and hybridized to the The GeneChip® Mouse Genome 430 2.0 Array in accordance to the Affymetrix GeneChip expression analysis technical manual (Affymetrix, Santa Clara, CA). After hybridization, arrays were washed and stained with Affymetrix fluidics protocol FS450_0001 and scanned with a 7G Affymetrix GeneChip Scanner. Image data were analyzed with Affymetrix Expression Console™ software and normalized with Robust Multichip Analysis (RMA; www.bioconductor.org/) to determine signal log ratios (CITE: Gentleman, R.C., Carey, V.J., Bates, D.M., Bolstad, B., Dettling, M., Dudoit, S., Ellis, B., Gautier, L., Ge, Y., Gentry, J., et al. (2004). Bioconductor: open software development for computational biology and bioinformatics. Genome Biol 5, R80.). The mean fold change was calculated from 3 independent technical replicates for each of the four experimental conditions and assessed by a non-parametric rank product test (CITE: Hong, F., Breitling, R., McEntee, C.W., Wittner, B.S., Nemhauser, J.L., and Chory, J. (2006). RankProd: a bioconductor package for detecting differentially expressed genes in meta-analysis. Bioinformatics 22, 2825-2827). Heat maps were generated with Genesis (Cite: Sturn, A., Quackenbush, J. and Trajanoski, Z. (2002) Genesis: cluster analysis of microarray data. Bioinformatics, 18, 207-208).
2013-01-01 | E-GEOD-37191 | biostudies-arrayexpress
Project description:Mast cells are hematopoietic cells that reside preferentially in tissues exposed to internal and external environments. Mast cells sense immunological, inflammatory and environmental stimuli, and can be activated to release granules and generate inflammatory mediators. Mast cell-derived products confer protection against snake venoms and some parasite infections. Aberrant activation of mast cells is a major contributor to human pathology, including allergy, asthma and adverse drug reactions. Their strict tissue location has largely impeded the isolation of large numbers of primary mast cell for further analysis. To better understand the biology of mast cells, we analyzed the proteome of primary human and mouse mast cells by quantitative mass spectrometry. We identified a mast cell-specific protein signature that was conserved from mouse to man. Compared to a comprehensive set of other immune cell lineages, proteome analysis identified a unique and distant mast cell cluster. The mast cell signature included proteins governing granule biosynthesis and secretion, as well as proteoglycan- and neurotransmitter metabolism. Proteome conservation across species suggests evolutionary maintenance of mast cell functions.
2020-02-12 | PXD014978 | Pride