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Helminths are multicellular parasites that are a substantial problem for both human and veterinary medicine. According to estimates, 1.5 billion people suffer from their infection, resulting in decreased life quality and burdens for healthcare systems. On the other hand, these infections may alleviate autoimmune diseases and allergy symptoms. The immune system is programmed to combat infections; nevertheless, its effector mechanisms may result in immunopathologies and exacerbate clinical symptoms. This review summarizes the role of the immune response against worms, with an emphasis on the Th2 response, which is a hallmark of helminth infections. We characterize non-immune cells (enteric tuft cells—ETCs) responsible for detecting parasites, as well as the role of hematopoietic-derived cells (macrophages, basophils, eosinophils, neutrophils, innate lymphoid cells group 2—ILC2s, mast cells, T cells, and B cells) in initiating and sustaining the immune response, as well as the functions they play in granulomas. The aim of this paper is to review the existing knowledge regarding the immune response against helminths, to attempt to decipher the interactions between cells engaged in the response, and to indicate the gaps in the current knowledge. [ABSTRACT FROM AUTHOR]

In the presence of orthopedic implants, opportunistic pathogens can easily colonize the biomaterial surfaces, forming protective biofilms. Life in biofilm is a central pathogenetic mechanism enabling bacteria to elude the host immune response and survive conventional medical treatments. The formation of mature biofilms is universally recognized as the main cause of septic prosthetic failures. Neutrophils are the first leukocytes to be recruited at the site of infection. They are highly efficient in detecting and killing planktonic bacteria. However, the interactions of these fundamental effector cells of the immune system with the biofilm matrix, which is the true interface of a biofilm with the host cells, have only recently started to be unveiled and are still to be fully understood. Biofilm matrix macromolecules consist of exopolysaccharides, proteins, lipids, teichoic acids, and the most recently described extracellular DNA. The latter can also be stolen from neutrophil extracellular traps (NETs) by bacteria, who use it to strengthen their biofilms. This paper aims to review the specific interactions that neutrophils develop when they physically encounter the matrix of a biofilm and come to interact with its polymeric molecular components. [ABSTRACT FROM AUTHOR]

Neutrophilia and the production of neutrophil extracellular traps (NETs) are two of many measures of increased inflammation in severe COVID-19 that also accompany its autoimmune complications, including coagulopathies, myocarditis and multisystem inflammatory syndrome in children (MIS-C). This paper integrates currently disparate measures of innate hyperactivation in severe COVID-19 and its autoimmune complications, and relates these to SARS-CoV-2 activation of innate immunity. Aggregated data include activation of Toll-like receptors (TLRs), nucleotide-binding oligomerization domain (NOD) receptors, NOD leucine-rich repeat and pyrin-domain-containing receptors (NLRPs), retinoic acid-inducible gene I (RIG-I) and melanoma-differentiation-associated gene 5 (MDA-5). SARS-CoV-2 mainly activates the virus-associated innate receptors TLR3, TLR7, TLR8, NLRP3, RIG-1 and MDA-5. Severe COVID-19, however, is characterized by additional activation of TLR1, TLR2, TLR4, TLR5, TLR6, NOD1 and NOD2, which are primarily responsive to bacterial antigens. The innate activation patterns in autoimmune coagulopathies, myocarditis and Kawasaki disease, or MIS-C, mimic those of severe COVID-19 rather than SARS-CoV-2 alone suggesting that autoimmunity follows combined SARS-CoV-2-bacterial infections. Viral and bacterial receptors are known to synergize to produce the increased inflammation required to support autoimmune disease pathology. Additional studies demonstrate that anti-bacterial antibodies are also required to account for known autoantigen targets in COVID-19 autoimmune complications. [ABSTRACT FROM AUTHOR]

Platelet–endothelial interactions have a critical role in microcirculatory function, which maintains tissue homeostasis. The subtle equilibrium between platelets and the vessel wall is disturbed by the coronavirus disease 2019 (COVID-19), which affects all three components of Virchow's triad (endothelial injury, stasis and a hypercoagulable state). Endotheliitis, vasculitis, glycocalyx degradation, alterations in blood flow and viscosity, neutrophil extracellular trap formation and microparticle shedding are only few pathomechanisms contributing to endothelial damage and microthrombosis resulting in capillary plugging and tissue ischemia. In the following opinion paper, we discuss major pathological processes leading to microvascular endothelial activation and thrombosis formation as a possible major adverse factor driving the deterioration of patient disease course in severe COVID-19. [ABSTRACT FROM AUTHOR]

After an acute ischemic stroke (AIS), inflammatory processes are able to concomitantly induce both beneficial and detrimental effects. In this narrative review, we updated evidence on the inflammatory pathways and mediators that are investigated as promising therapeutic targets. We searched for papers on PubMed and MEDLINE up to August 2016. The terms searched alone or in combination were: ischemic stroke, inflammation, oxidative stress, ischemia reperfusion, innate immunity, adaptive immunity, autoimmunity. Inflammation in AIS is characterized by a storm of cytokines, chemokines, and Damage-Associated Molecular Patterns (DAMPs) released by several cells contributing to exacerbate the tissue injury both in the acute and reparative phases. Interestingly, many biomarkers have been studied, but none of these reflected the complexity of systemic immune response. Reperfusion therapies showed a good efficacy in the recovery after an AIS. New therapies appear promising both in pre-clinical and clinical studies, but still need more detailed studies to be translated in the ordinary clinical practice. In spite of clinical progresses, no beneficial long-term interventions targeting inflammation are currently available. Our knowledge about cells, biomarkers, and inflammatory markers is growing and is hoped to better evaluate the impact of new treatments, such as monoclonal antibodies and cell-based therapies. [ABSTRACT FROM AUTHOR]

One role of neutrophils, the most abundant innate immune sentinels, is neutrophil extracellular trap (NET) formation, which plays a significant role in immune surveillance. However, NET operation is bidirectional. Recent studies report that NETs may contribute to the development of autoimmune diseases such as psoriasis. The participation of neutrophils in the pathogenesis of that disease is dependent on an autoinflammatory feedback loop between neutrophils, lymphocytes, dendritic cells and keratinocytes. Our aim was to clarify the field of NET research in psoriasis and highlight the main factors required for NET generation, which may be a target of new therapies. This article presents a comphrehensive review concerning studies addressing the participation of neutrophils in the pathogenesis of psoriasis. Based on the available English-language literature, we discuss original papers presenting significant research findings which may help to understand and interpret the NET formation process in psoriasis, as well as the newest systematic reviews on PubMed. Next, the comparison, synthesis and summary of reported results were performed to clearly indicate the specific component of the NET which participates in the development of psoriasis. [ABSTRACT FROM AUTHOR]

Diacylglycerol kinases (DGKs) play a key role in phosphoinositide signaling by removing diacylglycerol and generating phosphatidic acid. Besides the well-documented role of DGKα and DGKζ as negative regulators of lymphocyte responses, a robust body of literature points to those enzymes, and specifically DGKα, as crucial regulators of leukocyte function. Upon neutrophil stimulation, DGKα activation is necessary for migration and a productive response. The role of DGKα in neutrophils is evidenced by its aberrant behavior in juvenile periodontitis patients, which express an inactive DGKα transcript. Together with in vitro experiments, this suggests that DGKs may represent potential therapeutic targets for disorders where inflammation, and neutrophils in particular, plays a major role. In this paper we focus on obstructive respiratory diseases, including asthma and chronic obstructive pulmonary disease (COPD), but also rare genetic diseases such as alpha-1-antitrypsin deficiency. Indeed, the biological role of DGKα is understudied outside the T lymphocyte field. The recent wave of research aiming to develop novel and specific inhibitors as well as KO mice will allow a better understanding of DGK's role in neutrophilic inflammation. Better knowledge and pharmacologic tools may also allow DGK to move from the laboratory bench to clinical trials. [ABSTRACT FROM AUTHOR]