Updates on NET formation in health and disease

Leppkes, Moritz; Schick, Maximilian; Hohberger, Bettina; Mahajan, Aparna; Knopf, Jasmin; Schett, Georg; Muñoz, Luis; Herrmann, Martin

doi:10.1016/j.semarthrit.2019.09.011

Cited by 15 publications

(12 citation statements)

References 56 publications

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“…The “neutrophil swarming” is linked to another physiological defense mechanism that can promote autoantigen exposure, i.e., the aforementioned NET formation or NETosis [ 104 , 105 ]. In fact, when high numbers of neutrophils or neutrophil clusters are present, NET formation occurs in an aggregated fashion [ 106 ] that could aggravate a potentially autoantigenic exposure. In terms of the two main ANCA antigens in AAV, NET has been demonstrated as being primarily loaded with perinuclear ANCA antigens such as MPO but not PR3 [ 107 ]; thus, for the exposition of PR3 as autoantigen, NET or NETosis can be considered of lesser relevance.…”

Section: Cells Molecules and Mechanisms Of The Innate Immune Response Fuel The Granulomatous Inflammation In Gpamentioning

confidence: 99%

Granulomatous Inflammation in ANCA-Associated Vasculitis

Müller

Krause

Kerstein-Stähle

et al. 2021

IJMS

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ANCA-associated vasculitis (AAV) comprises granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). While systemic vasculitis is a hallmark of all AAV, GPA is characterized by extravascular granulomatous inflammation, preferentially affecting the respiratory tract. The mechanisms underlying the emergence of neutrophilic microabscesses; the appearance of multinucleated giant cells; and subsequent granuloma formation, finally leading to scarred or destroyed tissue in GPA, are still incompletely understood. This review summarizes findings describing the presence and function of molecules and cells contributing to granulomatous inflammation in the respiratory tract and to renal inflammation observed in GPA. In addition, factors affecting or promoting the development of granulomatous inflammation such as microbial infections, the nasal microbiome, and the release of damage-associated molecular patterns (DAMP) are discussed. Further, on the basis of numerous results, we argue that, in situ, various ways of exposure linked with a high number of infiltrating proteinase 3 (PR3)- and myeloperoxidase (MPO)-expressing leukocytes lower the threshold for the presentation of an altered PR3 and possibly also of MPO, provoking the local development of ANCA autoimmune responses, aided by the formation of ectopic lymphoid structures. Although extravascular granulomatous inflammation is unique to GPA, similar molecular and cellular patterns can be found in both the respiratory tract and kidney tissue of GPA and MPA patients; for example, the antimicrobial peptide LL37, CD163+ macrophages, or regulatory T cells. Therefore, we postulate that granulomatous inflammation in GPA or PR3-AAV is intertwined with autoimmune and destructive mechanisms also seen at other sites.

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Section: Cells Molecules and Mechanisms Of The Innate Immune Response Fuel The Granulomatous Inflammation In Gpamentioning

confidence: 99%

Granulomatous Inflammation in ANCA-Associated Vasculitis

Müller

Krause

Kerstein-Stähle

et al. 2021

IJMS

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“…Platelets are the main source of circulating exosomes ( Ogura et al, 2001 ). Platelet-derived exosomes containing HMGB1, miR-15b-5p and miR-378a-3p induce excessive neutrophil extracellular trap (NET) formation through Akt/mTOR autophagy pathway ( Jiao et al, 2020 ), which aggravates vascular endothelial injury and coagulation dysfunction ( Caudrillier et al, 2012 ; Leppkes et al, 2019 ).…”

Section: Effects Of Exosomes On Immune Cells In Sepsismentioning

confidence: 99%

Exosome: The Regulator of the Immune System in Sepsis

et al. 2021

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Sepsis is a syndrome comprised of a series of life-threatening organ dysfunctions caused by a maladjusted body response to infection with no effective treatment. There is growing evidence that the immune system plays a core role in sepsis. Pathogens cause abnormal host immune response and eventually lead to immunosuppression, which is an important cause of death in patients with sepsis. Exosomes are vesicles derived from double invagination of plasma membrane, associating with immune responses closely. The cargos delivered by exosomes into recipient cells, especially immune cells, effectively alter their response and functions in sepsis. In this review, we focus on the effects and mechanisms of exosomes on multiple immune cells, as well as the role of immune cell-derived exosomes in sepsis. This is helpful for us to have an in-depth understanding of the mechanism of immune disorders in sepsis. Exosomes is also expected to become a novel target and therapeutic approach for sepsis.

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“…The ocular surface comprises the cornea, conjunctiva and tear film, where antibodies, the complement system and innate immune cells participate in the defense against external stimuli [167]. The oral mucosa is among the most colonized surfaces by the microbiota, where cytokines, chemokines and salivary proteins, such as secretory IgA, IgG, lysozyme and mucins, as well as immune cells, such as neutrophils, macrophages and dendritic cells, maintain a balance between the oral commensals and the host [168,169].…”

Section: Nets In Other Mucosal Surfacesmentioning

confidence: 99%

To Trap a Pathogen: Neutrophil Extracellular Traps and Their Role in Mucosal Epithelial and Skin Diseases

Domínguez-Díaz

Varela-Trinidad

Muñoz-Sánchez

et al. 2021

Cells

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Neutrophils are the most abundant circulating innate immune cells and comprise the first immune defense line, as they are the most rapidly recruited cells at sites of infection or inflammation. Their main microbicidal mechanisms are degranulation, phagocytosis, cytokine secretion and the formation of extracellular traps. Neutrophil extracellular traps (NETs) are a microbicidal mechanism that involves neutrophil death. Since their discovery, in vitro and in vivo neutrophils have been challenged with a range of stimuli capable of inducing or inhibiting NET formation, with the objective to understand its function and regulation in health and disease. These networks composed of DNA and granular components are capable of immobilizing and killing pathogens. They comprise enzymes such as myeloperoxidase, elastase, cathepsin G, acid hydrolases and cationic peptides, all with antimicrobial and antifungal activity. Therefore, the excessive formation of NETs can also lead to tissue damage and promote local and systemic inflammation. Based on this concept, in this review, we focus on the role of NETs in different infectious and inflammatory diseases of the mucosal epithelia and skin.

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Updates on NET formation in health and disease

Cited by 15 publications

References 56 publications

Granulomatous Inflammation in ANCA-Associated Vasculitis

Granulomatous Inflammation in ANCA-Associated Vasculitis

Exosome: The Regulator of the Immune System in Sepsis

To Trap a Pathogen: Neutrophil Extracellular Traps and Their Role in Mucosal Epithelial and Skin Diseases

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