Human CD8+ T Cells Release Extracellular Traps Co-Localized With Cytotoxic Vesicles That Are Associated With Lesion Progression and Severity in Human Leishmaniasis

Koh, Carolina Cattoni; Wardini, Amanda Brito; Vieira, Millene; Passos, Lívia Silva Araújo; Martinelli, Patrícia Massara; Neves, Eula G. A.; Antonelli, Lis R. V.; Barbosa, Daniela Faria; Velikkakam, Teresiama; Gutseit, Eduardo; Menezes, Gustavo B.; Giunchetti, Rodolfo Cordeiro; Machado, Paulo Roberto Lima; Carvalho, Edgar M.; Gollob, Kenneth J.; Dutra, Walderez Ornelas

doi:10.3389/fimmu.2020.594581

Cited by 17 publications

(25 citation statements)

References 64 publications

(122 reference statements)

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“…The characterization of LETs formation in activated T lymphocytes was subsequently published for both CD4+ T cells [32,203] and CD8+ T cells [32], and with this description of LETs formation, another function was associated with a plethora of important functions of lymphocytes.…”

Section: Lymphocytesmentioning

confidence: 98%

“…Concerning infectious diseases, releasing ETs into the extracellular environment promotes the capture and death of the surrounding microorganisms [27][28][29][30][31]. Moreover, the presence of DNA and other proteins can lead to an increment in local inflammation, including exacerbation of the disease [10,32]. Even so, it has been described that the evasion of microorganisms by DNase production, the inhibition of cell recruitment from the immune response, as well as the evasion of bacteria by modification of the cell wall with alteration of the ionic charge, hampers the coupling of the microorganism to ETs (reviewed by the authors of [33]).…”

Section: Figurementioning

confidence: 99%

“…Nevertheless, many questions need to be clarified, although the first results point to the possibility that DNA extravasation plays a role in infectious and non-infectious diseases, especially in autoimmune diseases. According to the authors, the phenomenon has been named differently, but the term lymphocyte-derived extracellular traps (LETs) has now been used, and will, therefore, be referred to in this document [32].…”

Section: Lymphocytesmentioning

confidence: 99%

“…Koh et al has recently identified that after in vitro stimulation with anti-CD4/anti-CD28, CD4+ cells produce diffuse ETs that surround the cell like a halo and with evidence of cell death, and that this formation differs from ETs in CD8+ T lymphocytes, whose ETs form filaments [32].…”

Section: Lymphocytesmentioning

confidence: 99%

“…Subsequently, the granular content is released into the area of contact between the cells and the action of enzymes in a cascade of events that result in nuclear DNA degradation and the rupture of the plasma membrane, leading to cell destruction. This classic mechanism of CTL was added to the description of ETs production by CD8+ T lymphocytes by Koh et al, who evaluated LETs formation by CD8+ T lymphocytes both in vitro by stimulation with anti-CD3/anti-CD28 and in vivo in ATL lesions [32]. The authors detected the formation of long filaments of extracellular DNA containing enzymes of granular content shown by the colocalization of CD107a, resulting in cell death by LETs.…”

Section: Lymphocytesmentioning

confidence: 99%

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

Conceição-Silva

Reis

Luca

et al. 2021

Cells

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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.

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Section: Lymphocytesmentioning

confidence: 98%

Section: Figurementioning

confidence: 99%

Section: Lymphocytesmentioning

confidence: 99%

Section: Lymphocytesmentioning

confidence: 99%

Section: Lymphocytesmentioning

confidence: 99%

See 3 more Smart Citations

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

Conceição-Silva

Reis

Luca

et al. 2021

Cells

View full text Add to dashboard Cite

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Balancing the functions of DNA extracellular traps in intracellular parasite infections: implications for host defense, disease pathology and therapy

2023

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The release of DNA to the extracellular milieu is a biological process referred to as etosis, which is involved in both physiological and pathological functions. Although the release of DNA extracellular traps (ETs) was initially attributed to innate immune cells such as neutrophils, eosinophils, and macrophages, recent studies have shown that T cells, as well as non-immune cells, are capable of releasing ETs. These structures were described primarily for their potential to trap and kill pathogens, presenting an important strategy of host defense. Intriguingly, these functions have been associated with intracellular pathogens such as the parasites Leishmania sp. and Trypanosoma cruzi, causative agents of leishmaniasis and Chagas disease, respectively. These are two devastating tropical diseases that lead to thousands of deaths every year. In an apparent contradiction, ETs can also induce and amplify inflammation, which may lead to worsening disease pathology. This has prompted the concept of targeting ETs’ release as a means of controlling tissue destruction to treat human diseases. What is the best approach to prevent disease severity: inducing ETs to kill pathogens or preventing their release? In this Perspective article, we will discuss the importance of understanding ETs released by different cell types and the need to balance their potentially complementary functions. In addition, we will explore other functions of ETs and their translational applications to benefit individuals infected with intracellular parasites and other pathogens. Ultimately, a better understanding of the role of ETs in disease pathogenesis will provide valuable insights into developing novel therapies for human diseases.

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Pathogenesis of pneumonia and acute lung injury

2022

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Pneumonia and its sequelae, acute lung injury, present unique challenges for pulmonary and critical care healthcare professionals, and these challenges have recently garnered global attention due to the ongoing Sars-CoV-2 pandemic. One limitation to translational investigation of acute lung injury, including its most severe manifestation (acute respiratory distress syndrome, ARDS) has been heterogeneity resulting from the clinical and physiologic diagnosis that represents a wide variety of etiologies. Recent efforts have improved our understanding and approach to heterogeneity by defining sub-phenotypes of ARDS although significant gaps in knowledge remain. Improving our mechanistic understanding of acute lung injury and its most common cause, infectious pneumonia, can advance our approach to precision targeted clinical interventions. Here, we review the pathogenesis of pneumonia and acute lung injury, including how respiratory infections and lung injury disrupt lung homoeostasis, and provide an overview of respiratory microbial pathogenesis, the lung microbiome, and interventions that have been demonstrated to improve outcomes—or not—in human clinical trials.

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Human CD8+ T Cells Release Extracellular Traps Co-Localized With Cytotoxic Vesicles That Are Associated With Lesion Progression and Severity in Human Leishmaniasis

Cited by 17 publications

References 64 publications

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

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

Balancing the functions of DNA extracellular traps in intracellular parasite infections: implications for host defense, disease pathology and therapy

Pathogenesis of pneumonia and acute lung injury

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