Reaktionsmuster der lokoregionären Lymphknoten im Abflussgebiet von COVID-19-Lungen

Haslbauer, Jasmin D.; Matter, Matthias S.; Stalder, Anna K.; Tzankov, Alexandar

doi:10.1007/s00292-021-00914-z

Cited by 4 publications

(3 citation statements)

References 54 publications

(105 reference statements)

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“…As previously described in systematic histomorphological analyses on the same autopsy cohort ( 6 ), pulmonary draining lymph nodes of lethal COVID-19 displayed the following characteristics compared to controls: 1. vascular changes such as capillary stasis and edema (moderate-extensive 20/21 vs. 5/14; p=0.015) and presence of fibrin microthrombi (6/19 vs. 0/14; p=0.027) ( Figure 1A ); 2. absence or paucity of germinal centers (16/21 vs. 4/14; p=0.013) ( Figure 1B ); 3. increased extrafollicular accumulation of plasmablasts (accumulation in 8/21 vs. 1/14; p=0.05) ( Figure 1C ); 4. an overall increased presence of histiocytes with hemophagocytic activity (moderate-extensive 6/21 vs. 3/14; p=0.037) ( Figure 1D ).…”

Section: Resultsmentioning

confidence: 62%

“…Initial autopsy series have revealed characteristic histomorphology in lymph nodes of severe COVID-19, demarcating it from other viral infections. Predominant features included marked capillary congestion and edema, as well as paracortical increase of plasmablasts, a population of extrafollicular IgG and particularly IgM positive B-blasts, lacking germinal center formation, a predominance of M2-polarized macrophages and hemophagocytic lymphohistiocytosis (HLH) ( 6 , 7 ). Follicular hyperplasia, the histological correlate of an adequate immune response with immunologic memory, was rarely observed, replaced by an expansion of the abovementioned plasmablasts indicative of a transient humoral response in the absence of germinal center formation ( 8 , 9 ).…”

Section: Introductionmentioning

confidence: 99%

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Vascular Damage, Thromboinflammation, Plasmablast Activation, T-Cell Dysregulation and Pathological Histiocytic Response in Pulmonary Draining Lymph Nodes of COVID-19

et al. 2021

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Although initial immunophenotypical studies on peripheral blood and bronchoalveolar lavage samples have provided a glimpse into the immunopathology of COVID-19, analyses of pulmonary draining lymph nodes are currently scarce. 22 lethal COVID-19 cases and 28 controls were enrolled in this study. Pulmonary draining lymph nodes (mediastinal, tracheal, peribronchial) were collected at autopsy. Control lymph nodes were selected from a range of histomorphological sequelae [unremarkable histology, infectious mononucleosis, follicular hyperplasia, non-SARS related HLH, extrafollicular plasmablast activation, non-SARS related diffuse alveolar damage (DAD), pneumonia]. Samples were mounted on a tissue microarray and underwent immunohistochemical staining for a selection of immunological markers and in-situ hybridization for Epstein Barr Virus (EBV) and SARS-CoV-2. Gene expression profiling was performed using the HTG EdgeSeq Immune Response Panel. Characteristic patterns of a dysregulated immune response were detected in COVID-19: 1. An accumulation of extrafollicular plasmablasts with a relative paucity or depletion of germinal centers. 2. Evidence of T-cell dysregulation demonstrated by immunohistochemical paucity of FOXP3+, Tbet+ and LEF1+ positive T-cells and a downregulation of key genes responsible for T-cell crosstalk, maturation and migration as well as a reactivation of herpes viruses in 6 COVID-19 lymph nodes (EBV, HSV). 3. Macrophage activation by a M2-polarized, CD163+ phenotype and increased incidence of hemophagocytic activity. 4. Microvascular dysfunction, evidenced by an upregulation of hemostatic (CD36, PROCR, VWF) and proangiogenic (FLT1, TEK) genes and an increase of fibrin microthrombi and CD105+ microvessels. Taken together, these findings imply widespread dysregulation of both innate and adoptive pathways with concordant microvascular dysfunction in severe COVID-19.

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Section: Resultsmentioning

confidence: 62%

Section: Introductionmentioning

confidence: 99%

Vascular Damage, Thromboinflammation, Plasmablast Activation, T-Cell Dysregulation and Pathological Histiocytic Response in Pulmonary Draining Lymph Nodes of COVID-19

et al. 2021

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“…The aberrant organization of B-dependent zones, resulting in poor humoral immune response in patients with severe acute COVID-19, was noted in numerous studies [ 89 ]. The number of follicular dendritic cells, Bcl-6+ Tfh, and B-cells decreased in lymph nodes, whereas AID+ B-cell level was preserved most often [ 90 ].…”

Section: Resultsmentioning

confidence: 99%

Tuberculosis and COVID-19 Dually Affect Human Th17 Cell Immune Response

et al. 2023

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COVID-19 infection not only profoundly impacts the detection of tuberculosis infection (Tbc) but also affects modality in tuberculosis patient immune response. It is important to determine immune response alterations in latent tuberculosis infection as well as in SARS-CoV-2-infected tuberculosis patients. Such changes may have underlying effects on the development and course of further tuberculosis. Here, we aimed to review the characteristics of immune response in TB patients or convalescent COVID-19 patients with latent TB infection (LTBI). Materials and Methods. We analyzed the features of immune response in tuberculosis and COVID-19 patients. For this, we analyzed publications released from December 2019 to March 2023; those which were published in accessible international databases (“Medline”, “PubMed”, “Scopus”) and with keywords such as “COVID-19”, “SARS-CoV-2”, “tuberculosis”, “pulmonary tuberculosis”, “latent tuberculosis infection”, “Treg”, “follicular Treg”, and “Treg subsets”, we considered. Results. Through our analysis, we found that tuberculosis patients who had been infected with COVID-19 previously and elevated Th1 and Th2 cell levels. High levels of Th1 and Th2 cells may serve as a positive marker, characterizing activated immune response during TB infection. COVID-19 or post-COVID-19 subjects showed decreased Th17 levels, indicating a lack of tuberculosis development. Moreover, the typical course of tuberculosis is associated with an increase in Treg level, but COVID-19 contributes to a hyperinflammatory response. Conclusion. According to the data obtained, the course of tuberculosis proceeds in a dissimilar way due to the distinct immune response, elicited by SARS-CoV-2. Importantly, the development of active tuberculosis with a severe course is associated with a decline in Treg levels. Both pathogens lead to disturbed immune responses, increasing the risk of developing severe TB. The insights and findings of this paper may be used to improve the future management of individuals with latent and active tuberculosis.

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Lymph node stromal cells: subsets and functions in health and disease

Grasso

Pierie

Mebius

et al. 2021

Trends in Immunology

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Lymph nodes (LNs) aid the interaction between lymphocytes and antigenpresenting cells, resulting in adequate and prolonged adaptive immune responses. LN stromal cells (LNSCs) are crucially involved in steering adaptive immune responses at different levels. Most knowledge on LNSCs has been obtained from mouse studies, and few studies indicate similarities with their human counterparts. Recent advances in single-cell technologies have revealed significant LNSC heterogeneity among different subsets with potential selective functions in immunity. This review provides an overview of current knowledge of LNSCs based on human and murine studies describing the role of these cells in health and disease. LNSCs as orchestrators of the immune systemLNs are specialized secondary lymphoid organs (SLOs) that are essential for the initiation of adaptive immunity. Most cells within LNs are lymphocytes that continuously enter the LN from the bloodstream. The afferent lymph transports antigens and antigen-presenting cells (APCs; see Glossary) to the LN, which creates an environment in which antigen-specific lymphocytes and APCs can optimally interact, resulting in adequate and prolonged immune responses [1]. The architecture of the LN is pivotal for its role in inducing humoral immune responses, and this is created and supported by LNSCs (Box 1) [2]. LNSCs create a 3D network that generates a backbone for immune cells to migrate on, and thus, during the time lymphocytes reside in the LN, they extensively interact with stromal cells. In addition to providing structural support, LNSCs also provide survival signals, nutrients, soluble factors, and antigens that are collectively required for immunosurveillance as well as for the generation and control of adaptive immune responses [3,4]. Therefore, understanding the immunobiology of LNSCs is key to comprehending specific aspects of the immune system more fully. The aim of this review is to provide an overview of the current state of knowledge about murine and human LNSC subsets and functions. We discuss recent findings regarding human and mouse LNSCs under homeostatic conditions, and describe their immunomodulatory capacities during autoimmunity, infection, and cancer. We anticipate that some of these findings may fuel further investigations into the field of LN biology and immune defense across species. HighlightsSingle-cell RNA sequencing has uncovered conspicuous heterogeneity in lymph node stromal cells (LNSCs) populations in mice and humans.Human and mouse LNSC subsets show similarities in their transcriptomic profiles and trajectory analyses.Each LNSC subset has its own specific function in regulating immune responses.Human LNSCs have the machinery to regulate peripheral tolerance, making them attractive targets for modulating tolerance induction and maintenance.LNSCs in mice and humans can suppress T cell proliferation during strong inflammatory stimuli. Different mechanisms are utilized to perform this function.LNSCs from patients with particular autoimmune diseases exhibit alte...

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Reaktionsmuster der lokoregionären Lymphknoten im Abflussgebiet von COVID-19-Lungen

Cited by 4 publications

References 54 publications

Vascular Damage, Thromboinflammation, Plasmablast Activation, T-Cell Dysregulation and Pathological Histiocytic Response in Pulmonary Draining Lymph Nodes of COVID-19

Vascular Damage, Thromboinflammation, Plasmablast Activation, T-Cell Dysregulation and Pathological Histiocytic Response in Pulmonary Draining Lymph Nodes of COVID-19

Tuberculosis and COVID-19 Dually Affect Human Th17 Cell Immune Response

Lymph node stromal cells: subsets and functions in health and disease

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