Clarissa S M Reis

Bio: Clarissa S M Reis is an academic researcher from Oswaldo Cruz Foundation. The author has contributed to research in topics: Immune system. The author has an hindex of 1, co-authored 1 publications receiving 2 citations.

The Immune System Throws Its Traps: Cells and Their Extracellular Traps in Disease and Protection.

Abstract: The first formal description of the microbicidal activity of extracellular traps (ETs) containing DNA occurred in neutrophils in 2004. Since then, ETs have been identified in different populations of cells involved in both innate and adaptive immune responses. Much of the knowledge has been obtained from in vitro or ex vivo studies; however, in vivo evaluations in experimental models and human biological materials have corroborated some of the results obtained. Two types of ETs have been described-suicidal and vital ETs, with or without the death of the producer cell. The studies showed that the same cell type may have more than one ETs formation mechanism and that different cells may have similar ETs formation mechanisms. ETs can act by controlling or promoting the mechanisms involved in the development and evolution of various infectious and non-infectious diseases, such as autoimmune, cardiovascular, thrombotic, and neoplastic diseases, among others. This review discusses the presence of ETs in neutrophils, macrophages, mast cells, eosinophils, basophils, plasmacytoid dendritic cells, and recent evidence of the presence of ETs in B lymphocytes, CD4+ T lymphocytes, and CD8+ T lymphocytes. Moreover, due to recently collected information, the effect of ETs on COVID-19 is also discussed.

Molecular Mechanisms of mtDNA-Mediated Inflammation

Abstract: Besides their role in cell metabolism, mitochondria display many other functions. Mitochondrial DNA (mtDNA), the own genome of the organelle, plays an important role in modulating the inflammatory immune response. When released from the mitochondrion to the cytosol, mtDNA is recognized by cGAS, a cGAMP which activates a pathway leading to enhanced expression of type I interferons, and by NLRP3 inflammasome, which promotes the activation of pro-inflammatory cytokines Interleukin-1beta and Interleukin-18. Furthermore, mtDNA can be bound by Toll-like receptor 9 in the endosome and activate a pathway that ultimately leads to the expression of pro-inflammatory cytokines. mtDNA is released in the extracellular space in different forms (free DNA, protein-bound DNA fragments) either as free circulating molecules or encapsulated in extracellular vesicles. In this review, we discussed the latest findings concerning the molecular mechanisms that regulate the release of mtDNA from mitochondria, and the mechanisms that connect mtDNA misplacement to the activation of inflammation in different pathophysiological conditions.

Basophils and Mast Cells in COVID-19 Pathogenesis.

Abstract: Basophils and mast cells are among the principal inducers of Th2 responses and have a crucial role in allergic and anti-parasitic protective immunity. Basophils can function as antigen-presenting cells that bind antigens on their surface and boost humoral immune responses, inducing Th2 cell differentiation. Their depletion results in lower humoral memory activation and greater infection susceptibility. Basophils seem to have an active role upon immune response to SARS-CoV-2. In fact, a coordinate adaptive immune response to SARS-CoV-2 is magnified by basophils. It has been observed that basophil amount is lower during acute disease with respect to the recovery phase and that the grade of this depletion is an important determinant of the antibody response to the virus. Moreover, mast cells, present in a great quantity in the nasal epithelial and lung cells, participate in the first immune response to SARS-CoV-2. Their activation results in a hyperinflammatory syndrome through the release of inflammatory molecules, participating to the “cytokine storm” and, in a longer period, inducing pulmonary fibrosis. The literature data suggest that basophil counts may be a useful prognostic tool for COVID-19, since their reduction is associated with a worse prognosis. Mast cells, on the other hand, represent a possible therapeutic target for reducing the airway inflammation characteristic of the hyperacute phase of the disease.

Role of macrophage extracellular traps in innate immunity and inflammatory disease.

Abstract: Macrophages play an integral role in initiating innate immune defences and regulating inflammation. They are also involved in maintaining homeostasis and the resolution of inflammation, by promoting tissue repair and wound healing. There is evidence that like neutrophils, macrophages can release extracellular traps following exposure to a range of pathogenic and pro-inflammatory stimuli. Extracellular traps are released by a specialised cell death pathway termed 'ETosis', and consist of a backbone of DNA and histones decorated with a range of other proteins. The composition of extracellular trap proteins can be influenced by both the cell type and the local environment in which the traps are released. In many cases, these proteins have an antimicrobial role and assist with pathogen killing. Therefore, the release of extracellular traps serves as a means to both immobilise and destroy invading pathogens. In addition to their protective role, extracellular traps are also implicated in disease pathology. The release of neutrophil extracellular traps (NETs) is causally linked to the development of wide range of human diseases. However, whether macrophage extracellular traps (METs) play a similar role in disease pathology is less well established. Moreover, macrophages are also involved in the clearance of extracellular traps, which could assist in the resolution of tissue damage associated with the presence of extracellular traps. In this review, we will provide an overview of the pathways responsible for macrophage extracellular trap release, and discuss the role of these structures in innate immunity and disease pathology and possible therapeutic strategies.

What is the impact of circulating histones in COVID-19: a systematic review

Abstract: Abstract The infectious respiratory condition COVID-19 manifests a clinical course ranging from mild/moderate up-to critical systemic dysfunction and death linked to thromboinflammation. During COVID-19 infection, neutrophil extracellular traps participating in cytokine storm and coagulation dysfunction have emerged as diagnostic/prognostic markers. The characterization of NET identified that mainly histones, have the potential to initiate and propagate inflammatory storm and thrombosis, leading to increased disease severity and decreased patient survival. Baseline assessment and serial monitoring of blood histone concentration may be conceivably useful in COVID-19. We performed a literature review to explore the association among increased circulating levels of histones, disease severity/mortality in COVID-19 patients, and comparison of histone values between COVID-19 and non-COVID-19 patients. We carried out an electronic search in Medline and Scopus, using the keywords “COVID-19” OR “SARS-CoV-2” AND “histone” OR “citrullinated histones” OR “hyperhistonemia”, between 2019 and present time (i.e., June 07th, 2022), which allowed to select 17 studies, totaling 1,846 subjects. We found that substantially elevated histone values were consistently present in all COVID-19 patients who developed unfavorable clinical outcomes. These findings suggest that blood histone monitoring upon admission and throughout hospitalization may be useful for early identification of higher risk of unfavorable COVID-19 progression. Therapeutic decisions in patients with SARS-CoV-2 based on the use of histone cut-off values may be driven by drugs engaging histones, finally leading to the limitation of cytotoxic, inflammatory, and thrombotic effects of circulating histones in viral sepsis.

Histones: The critical players in innate immunity

Abstract: The highly conserved histones in different species seem to represent a very ancient and universal innate host defense system against microorganisms in the biological world. Histones are the essential part of nuclear matter and act as a control switch for DNA transcription. However, histones are also found in the cytoplasm, cell membranes, and extracellular fluid, where they function as host defenses and promote inflammatory responses. In some cases, extracellular histones can act as damage-associated molecular patterns (DAMPs) and bind to pattern recognition receptors (PRRs), thereby triggering innate immune responses and causing initial organ damage. Histones and their fragments serve as antimicrobial peptides (AMPs) to directly eliminate bacteria, viruses, fungi, and parasites in vitro and in vivo. Histones are also involved in phagocytes-related innate immune response as components of neutrophil extracellular traps (NETs), neutrophil activators, and plasminogen receptors. In addition, as a considerable part of epigenetic regulation, histone modifications play a vital role in regulating the innate immune response and expression of corresponding defense genes. Here, we review the regulatory role of histones in innate immune response, which provides a new strategy for the development of antibiotics and the use of histones as therapeutic targets for inflammatory diseases, sepsis, autoimmune diseases, and COVID-19.