Neutrophil extracellular traps in patients with pulmonary tuberculosis

Meer, Anne Jan van der; Blok, Dana C.; Kager, Liesbeth M.; Lede, Ivar O.; Rahman, Waliur; Afroz, Rumana; Ghose, Aniruddha; Visser, Caroline E.; Zahed, Abu Shahed Md; Husain, Anwar; Alam, Khan Mashrequl; Barua, Pravat Chandra; Hassan, Mahtabuddin; Tayab, Abu; Dondorp, Arjen M.; Poll, Tom van der

doi:10.1186/s12931-017-0663-1

Cited by 21 publications

(19 citation statements)

References 17 publications

(30 reference statements)

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“…[62] Higher KYNA level was reported in tick-borne encephalitis, schizophrenia, and HIV-related illness, and are known to create confusion and psychotic symptoms in humans. [65] Therefore, higher SERPINA1 in circulatory small EVs may provide defense to individuals that carry Mtb by countering infection with the higher NE levels to neutralize bacterial infection and promote neutrophil phagocytosis. Neutrophil elastase (NE) released from white blood cells fight infection and higher serum NE abundance was reported in tuberculosis patients.…”

Section: Discussionmentioning

confidence: 99%

Serum Small Extracellular Vesicles Proteome of Tuberculosis Patients Demonstrated Deregulated Immune Response

Arya

Dabral

Faruquee

et al. 2019

Proteomics Clinical Apps

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Purpose Detailed understanding of host pathogen interaction in tuberculosis is an important avenue for identifying novel therapeutic targets. Small extracellular vesicles (EVs) like exosomes that are rich in proteins, nucleic acids and lipids, act as messengers and may show altered composition in disease conditions. Experimental design In this case control study, small EVs are isolated from serum of 58 subjects (all male, 33 (15–70) in years) including drug naïve active tuberculosis (ATB: n = 22), non‐tuberculosis (NTB: n = 18), and healthy subjects (n = 18). Serum small EVs proteome analysis is carried out using isobaric tag for relative and absolute quantification (iTRAQ) experiments and an independent sample (n = 36) is used for validation. Results A set of 132 and 68 proteins are identified in iTRAQ‐I (ATB/Healthy) and iTRAQ‐II (ATB/NTB) experiments, respectively. Four proteins (KYAT3, SERPINA1, HP, and APOC3) show deregulation (log2‐fold change > ±0.48, p < 0.05) in ATB with respect to healthy controls and Western blot data corroborated mass spectrometry findings. Conclusions and clinical relevance These important proteins, involved in neutrophil degranulation, plasma heme scavenging, kynurenine, and lipid metabolism, show deregulation in ATB patients. Identification of such a protein panel in circulating small EVs besides providing novel insights into their role in tuberculosis may prove to be useful targets to develop host‐directed therapeutic intervention.

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Section: Discussionmentioning

confidence: 99%

Serum Small Extracellular Vesicles Proteome of Tuberculosis Patients Demonstrated Deregulated Immune Response

Arya

Dabral

Faruquee

et al. 2019

Proteomics Clinical Apps

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“…These adhesive interactions can form platelet-monocyte aggregates (PMA) and platelet-neutrophil aggregates (PNA) which lead to cell activation and enhance immune function such as cytokine or MMP production. Platelets can stimulate neutrophils to release neutrophil extracellular traps (NETs) ( 69 ), which are increased in the plasma of TB patients ( 70 ) and have been associated with severe TB-associated lung damage and subsequent sequelae ( 71 ). These adhesive interactions are mediated by the two main families of cell adhesion molecules, selectins and integrins.…”

Section: Platelet-leukocyte Signaling and Cellular Interactions In Tbmentioning

confidence: 99%

Platelet Activation and the Immune Response to Tuberculosis

2021

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In 2019 10 million people developed symptomatic tuberculosis (TB) disease and 1.2 million died. In active TB the inflammatory response causes tissue destruction, which leads to both acute morbidity and mortality. Tissue destruction in TB is driven by host innate immunity and mediated via enzymes, chiefly matrix metalloproteinases (MMPs) which are secreted by leukocytes and stromal cells and degrade the extracellular matrix. Here we review the growing evidence implicating platelets in TB immunopathology. TB patients typically have high platelet counts, which correlate with disease severity, and a hypercoagulable profile. Platelets are present in human TB granulomas and platelet-associated gene transcripts are increased in TB patients versus healthy controls. Platelets most likely drive TB immunopathology through their effect on other immune cells, particularly monocytes, to lead to upregulation of activation markers, increased MMP secretion, and enhanced phagocytosis. Finally, we consider current evidence supporting use of targeted anti-platelet agents in the treatment of TB due to growing interest in developing host-directed therapies to limit tissue damage and improve treatment outcomes. In summary, platelets are implicated in TB disease and contribute to MMP-mediated tissue damage via their cellular interactions with other leukocytes, and are potential targets for novel host-directed therapies.

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“…1 Because many of the antimicrobial contents of neutrophil extracellular traps (NETs) have intrinsic cytotoxic activity, they also have the potential to cause bystander injury to host cells. [3][4][5][6] However, more recent work has demonstrated that NETs also form in response to noninfectious tissue injury. [3][4][5][6] However, more recent work has demonstrated that NETs also form in response to noninfectious tissue injury.…”

Section: Introductionmentioning

confidence: 99%

“…2 In the lung, this has been suspected during infectious exacerbations of cystic fibrosis (CF), chronic pulmonary obstructive disease, bacterial pneumonia, and tuberculosis. [3][4][5][6] However, more recent work has demonstrated that NETs also form in response to noninfectious tissue injury. NETs have been reported to promote inflammation in models of primary lung graft dysfunction (PGD), 7 transfusion-related acute lung injury, 8 and ventilation-induced acute lung injury.…”

Section: Introductionmentioning

confidence: 99%

Neutrophil extracellular trap fragments stimulate innate immune responses that prevent lung transplant tolerance

Scozzi

Wang

Liao

et al. 2019

American Journal of Transplantation

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Neutrophil extracellular traps (NETs) have been shown to worsen acute pulmonary injury including after lung transplantation. The breakdown of NETs by DNAse‐1 can help restore lung function, but whether there is an impact on allograft tolerance remains less clear. Using intravital 2‐photon microscopy, we analyzed the effects of DNAse‐1 on NETs in mouse orthotopic lung allografts damaged by ischemia‐reperfusion injury. Although DNAse‐1 treatment rapidly degrades intragraft NETs, the consequential release of NET fragments induces prolonged interactions between infiltrating CD4+ T cells and donor‐derived antigen presenting cells. DNAse‐1 generated NET fragments also promote human alveolar macrophage inflammatory cytokine production and prime dendritic cells for alloantigen‐specific CD4+ T cell proliferation through activating toll‐like receptor (TLR) — Myeloid Differentiation Primary Response 88 (MyD88) signaling pathways. Furthermore, and in contrast to allograft recipients with a deficiency in NET generation due to a neutrophil‐specific ablation of Protein Arginine Deiminase 4 (PAD4), DNAse‐1 administration to wild‐type recipients promotes the recognition of allo‐ and self‐antigens and prevents immunosuppression‐mediated lung allograft acceptance through a MyD88‐dependent pathway. Taken together, these data show that the rapid catalytic release of NET fragments promotes innate immune responses that prevent lung transplant tolerance.

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Neutrophil extracellular traps in patients with pulmonary tuberculosis

Cited by 21 publications

References 17 publications

Serum Small Extracellular Vesicles Proteome of Tuberculosis Patients Demonstrated Deregulated Immune Response

Serum Small Extracellular Vesicles Proteome of Tuberculosis Patients Demonstrated Deregulated Immune Response

Platelet Activation and the Immune Response to Tuberculosis

Neutrophil extracellular trap fragments stimulate innate immune responses that prevent lung transplant tolerance

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