DAMPs, PAMPs, and LAMPs in Immunity and Sterile Inflammation

2020 ◽  
Vol 15 (1) ◽  
pp. 493-518 ◽  
Author(s):  
Joel Zindel ◽  
Paul Kubes
Keyword(s):  
Immune Cell ◽  
Inflammatory Diseases ◽  
Sterile Inflammation ◽  
Lifestyle Choices ◽  
Inflammatory Site ◽  
Specific Receptors ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
Killer T Cells ◽  
Invariant Natural Killer

Recognizing the importance of leukocyte trafficking in inflammation led to some therapeutic breakthroughs. However, many inflammatory pathologies remain without specific therapy. This review discusses leukocytes in the context of sterile inflammation, a process caused by sterile (non-microbial) molecules, comprising damage-associated molecular patterns (DAMPs). DAMPs bind specific receptors to activate inflammation and start a highly optimized sequence of immune cell recruitment of neutrophils and monocytes to initiate effective tissue repair. When DAMPs are cleared, the recruited leukocytes change from a proinflammatory to a reparative program, a switch that is locally supervised by invariant natural killer T cells. In addition, neutrophils exit the inflammatory site and reverse transmigrate back to the bloodstream. Inflammation persists when the program switch or reverse transmigration fails, or when the coordinated leukocyte effort cannot clear the immunostimulatory molecules. The latter causes inappropriate leukocyte activation, a driver of many pathologies associated with poor lifestyle choices. We discuss lifestyle-associated inflammatory diseases and their corresponding immunostimulatory lifestyle-associated molecular patterns (LAMPs) and distinguish them from DAMPs.

scholarly journals The COVIDome Explorer Researcher Portal

2021 ◽  
Author(s):  
Kelly D. Sullivan ◽  
Matthew D. Galbraith ◽  
Kohl T. Kinning ◽  
Kyle Bartsch ◽  
Nik Levinsky ◽  
...  
Keyword(s):  
Immune Cell ◽  
Mass Cytometry ◽  
C Reactive Protein ◽  
Data Annotation ◽  
Reactive Protein ◽  
Physiological Processes ◽  
Omics Analysis ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
Blood Transcriptome

SUMMARYCOVID-19 pathology involves dysregulation of diverse molecular, cellular, and physiological processes. In order to expedite integrated and collaborative COVID-19 research, we completed multi-omics analysis of hospitalized COVID-19 patients including matched analysis of the whole blood transcriptome, plasma proteomics with two complementary platforms, cytokine profiling, plasma and red blood cell metabolomics, deep immune cell phenotyping by mass cytometry, and clinical data annotation. We refer to this multidimensional dataset as the COVIDome. We then created the COVIDome Explorer, an online researcher portal where the data can be analyzed and visualized in real time. We illustrate here the use of the COVIDome dataset through a multi-omics analysis of biosignatures associated with C-reactive protein (CRP), an established marker of poor prognosis in COVID-19, revealing associations between CRP levels and damage-associated molecular patterns, depletion of protective serpins, and mitochondrial metabolism dysregulation. We expect that the COVIDome Explorer will rapidly accelerate data sharing, hypothesis testing, and discoveries worldwide.

scholarly journals Interplay between the immune system and adipose tissue in obesity

2014 ◽  
Vol 223 (2) ◽  
pp. R41-R48 ◽  
Author(s):  
Mark A Exley ◽  
Laura Hand ◽  
Donal O'Shea ◽  
Lydia Lynch
Keyword(s):  
T Cells ◽  
Adipose Tissue ◽  
Immune System ◽  
Immune Cell ◽  
Bioactive Molecules ◽  
Cell Repertoire ◽  
Alternatively Activated Macrophages ◽  
Killer T Cells ◽  
Invariant Natural Killer ◽  
Alternatively Activated

Obesity is a major risk factor for metabolic disease, with white adipose tissue (WAT) inflammation emerging as a key underlying pathology. Alongside its major role in energy storage, WAT is an important endocrine organ, producing many bioactive molecules, termed adipokines, which not only serve as regulators of systemic metabolism, but also possess immunoregulatory properties. Furthermore, WAT contains a unique immune cell repertoire, including an accumulation of leukocytes that are rare in other locations. These include alternatively activated macrophages, invariant natural killer T cells, and regulatory T cells. Disruption of resident adipose leukocyte homeostasis contributes to obesity-associated inflammation and consequent metabolic disorder. Despite many recent advances in this new field of immuno-metabolism, fundamental questions of why and how inflammation arises as obesity develops are not yet fully understood. Exploring the distinct immune system of adipose tissue is fundamental to our understanding of the endocrine as well as immune systems. In this review, we discuss the roles of adipose tissue leukocytes in the transition to obesity and progression of inflammation and highlight potential anti-inflammatory therapies for combating obesity-related pathology.

scholarly journals Pyroptosis in Cancer: Friend or Foe?

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3620
Author(s):  
Xiuxia Lu ◽  
Tianhui Guo ◽  
Xing Zhang
Keyword(s):  
Tumor Immunity ◽  
Inflammatory Diseases ◽  
Chemotherapeutic Drugs ◽  
T Cell Therapy ◽  
Car T Cell Therapy ◽  
Car T ◽  
Pore Forming Proteins ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Pyroptosis is an inflammatory form of programmed cell death that is mediated by pore-forming proteins such as the gasdermin family (GSDMs), including GSDMA-E. Upon cleavage by activated caspases or granzyme proteases, the N-terminal of GSDMs oligomerizes in membranes to form pores, resulting in pyroptosis. Though all the gasdermin proteins have been studied in cancer, the role of pyroptosis in cancer remains mysterious, with conflicting findings. Numerous studies have shown that various stimuli, such as pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), and chemotherapeutic drugs, could trigger pyroptosis when the cells express GSDMs. However, it is not clear whether pyroptosis in cancer induced by chemotherapeutic drugs or CAR T cell therapy is beneficial or harmful for anti-tumor immunity. This review discusses the discovery of pyroptosis as well as its role in inflammatory diseases and cancer, with an emphasis on tumor immunity.

scholarly journals Histone H3 Cleavage in Severe COVID-19 ICU Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Joram Huckriede ◽  
Femke de Vries ◽  
Michael Hultström ◽  
Kanin Wichapong ◽  
Chris Reutelingsperger ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Secondary Infection ◽  
Treatment Options ◽  
Histone H3 ◽  
Kidney Injury ◽  
Neutrophil Extracellular Trap ◽  
Icu Patients ◽  
Extracellular Histones ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

The severity of coronavirus disease 19 (COVID-19) is associated with neutrophil extracellular trap (NET) formation. During NET formation, cytotoxic extracellular histones are released, the presence of which is linked to the initiation and progression of several acute inflammatory diseases. Here we study the presence and evolution of extracellular histone H3 and several other neutrophil-related molecules and damage-associated molecular patterns (DAMPs) in the plasma of 117 COVID-19-positive ICU patients. We demonstrate that at ICU admission the levels of histone H3, MPO, and DNA-MPO complex were all significantly increased in COVID-19-positive patients compared to control samples. Furthermore, in a subset of 54 patients, the levels of each marker remained increased after 4+ days compared to admission. Histone H3 was found in 28% of the patients on admission to the ICU and in 50% of the patients during their stay at the ICU. Notably, in 47% of histone-positive patients, we observed proteolysis of histone in their plasma. The overall presence of histone H3 during ICU stay was associated with thromboembolic events and secondary infection, and non-cleaved histone H3 was associated with the need for vasoactive treatment, invasive ventilation, and the development of acute kidney injury. Our data support the validity of treatments that aim to reduce NET formation and additionally underscore that more targeted therapies focused on the neutralization of histones should be considered as treatment options for severe COVID-19 patients.

Pound the alarm: danger signals in rheumatic diseases

2014 ◽  
Vol 128 (5) ◽  
pp. 297-305 ◽  
Author(s):  
Steven O’Reilly
Keyword(s):  
Nuclear Factor Κb ◽  
Sterile Inflammation ◽  
Nuclear Factor ◽  
Danger Signals ◽  
Rheumatic Conditions ◽  
Molecular Patterns ◽  
Dying Cells ◽  
Damage Associated Molecular Patterns ◽  
Mediate Inflammation

Damage-associated molecular patterns (DAMPs) are chemically heterogeneous endogenous host molecules rapidly released from damaged or dying cells that incite a sterile inflammatory response mediated via pattern recognition receptors (PRRs). The sources of DAMPs are dead or dying cells or the extracellular matrix and can signal through the PRRs, the Toll-like receptors or cytosolic Nod-like receptors, culminating in nuclear factor κB (NF-κB) activation and pro-inflammatory cytokine secretion. Together, these molecules are involved in sterile inflammation and many are associated with rheumatic autoimmune diseases such as rheumatoid arthritis, systemic lupus erythromatosus, psoriatic arthritis and systemic sclerosis. These diseases are associated with inflammation and many danger signals are found in sites of sterile inflammation and mediate inflammation. The present review examines the role of DAMPs in rheumatic conditions and suggests avenues for their therapeutic modulation.

scholarly journals Nuclear Alarmin Cytokines in Inflammation

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Lili Jiang ◽  
Yijia Shao ◽  
Yao Tian ◽  
Changsheng Ouyang ◽  
Xiaohua Wang
Keyword(s):  
Inflammatory Response ◽  
Physiological Stress ◽  
Physiological State ◽  
High Mobility ◽  
Molecular Structures ◽  
Sterile Inflammation ◽  
Microbial Pathogens ◽  
Endogenous Proteins ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Pathogen-associated molecular patterns (PAMPs) are some nonspecific and highly conserved molecular structures of exogenous specific microbial pathogens, whose products can be recognized by pattern recognition receptor (PRR) on innate immune cells and induce an inflammatory response. Under physiological stress, activated or damaged cells might release some endogenous proteins that can also bind to PRR and cause a harmful aseptic inflammatory response. These endogenous proteins were named damage-associated molecular patterns (DAMPs) or alarmins. Indeed, alarmins can also play a beneficial role in the tissue repair in certain environments. Besides, some alarmin cytokines have been reported to have both nuclear and extracellular effects. This group of proteins includes high-mobility group box-1 protein (HMGB1), interleukin (IL)-33, IL-1α, IL-1F7b, and IL-16. In this article, we review the involvement of nuclear alarmins such as HMGB1, IL-33, and IL-1α under physiological state or stress state and suggest a novel activity of these molecules as central initiators in the development of sterile inflammation.

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