scholarly journals Longitudinal proteomic analysis of plasma from patients with severe COVID-19 reveal patient survival-associated signatures, tissue-specific cell death, and cell-cell interactions

2021 ◽  
pp. 100287
Author(s):  
Michael R. Filbin ◽  
Arnav Mehta ◽  
Alexis M. Schneider ◽  
Kyle R. Kays ◽  
Jamey R. Guess ◽  
...  
Author(s):  
Michael R. Filbin ◽  
Arnav Mehta ◽  
Alexis M. Schneider ◽  
Kyle R. Kays ◽  
Jamey R. Guess ◽  
...  

SummaryCOVID-19 has caused over 1 million deaths globally, yet the cellular mechanisms underlying severe disease remain poorly understood. By analyzing several thousand plasma proteins in 306 COVID-19 patients and 78 symptomatic controls over serial timepoints using two complementary approaches, we uncover COVID-19 host immune and non-immune proteins not previously linked to this disease. Integration of plasma proteomics with nine published scRNAseq datasets shows that SARS-CoV-2 infection upregulates monocyte/macrophage, plasmablast, and T cell effector proteins. By comparing patients who died to severely ill patients who survived, we identify dynamic immunomodulatory and tissue-associated proteins associated with survival, providing insights into which host responses are beneficial and which are detrimental to survival. We identify intracellular death signatures from specific tissues and cell types, and by associating these with angiotensin converting enzyme 2 (ACE2) expression, we map tissue damage associated with severe disease and propose which damage results from direct viral infection rather than from indirect effects of illness. We find that disease severity in lung tissue is driven by myeloid cell phenotypes and cell-cell interactions with lung epithelial cells and T cells. Based on these results, we propose a model of immune and epithelial cell interactions that drive cell-type specific and tissue-specific damage in severe COVID-19.


2021 ◽  
Vol 12 (1) ◽  
pp. 331-340
Author(s):  
Yiao Wang ◽  
Ozgun Kilic ◽  
Clifford M. Csizmar ◽  
Sudhat Ashok ◽  
James L. Hougland ◽  
...  

Multicellular biology is dependent on the control of cell-cell interactions. The prenylated antigen-targeted CSANs provide a general approach for the regulation of specific cell-cell interactions and will be valuable for a plethora of fundamental and therapeutic applications.


Author(s):  
Kiniwa Tsuyoshi ◽  
Kazuyo Moro

Abstract Group 2 innate lymphoid cells (ILC2s) are novel lymphocytes discovered in 2010. Unlike T or B cells, ILC2s are activated nonspecifically by environmental factors and produce various cytokines, thus playing a role in tissue homeostasis, diseases including allergic diseases, and parasite elimination. ILC2s were first reported as cells abundantly present in fat-associated lymphoid clusters in adipose tissue. However, subsequent studies revealed their presence in various tissues throughout the body, acting as key players in tissue-specific diseases. Recent histologic analyses revealed that ILC2s are concentrated in specific regions in tissues, such as the lamina propria and perivascular regions, with their function being controlled by the surrounding cells, such as epithelial cells and other immune cells, via cytokine and lipid production or by cell–cell interactions through surface molecules. Especially, some stromal cells are identified as the niche cells for ILC2s, both in the steady state and under inflammatory conditions, through the production of IL-33 or extracellular-matrix factors. Additionally, peripheral neurons reportedly co-localize with ILC2s and alter their function directly through neurotransmitters. These findings suggest that the different localizations or different cell–cell interactions might affect the function of ILC2s. Furthermore, generally, ILC2s are thought to be tissue-resident cells; however, they occasionally migrate to other tissues and perform a new role; this supports the importance of the microenvironment for their function. We summarize here the current understanding of how the microenvironment controls ILC2 localization and function with the aim of promoting the development of novel diagnostic and therapeutic methods.


2012 ◽  
Vol 347 (2) ◽  
pp. 343-356 ◽  
Author(s):  
Angela-Maria Meyer zum Gottesberge ◽  
Thomas Massing ◽  
Stefan Hansen

2021 ◽  
Author(s):  
Debangana Mukhopadhyay ◽  
Rumi De

Cellular aggregation is a complex process orchestrated by various kinds of interactions depending on its environments. Different interactions give rise to different pathways of cellular rearrangement and the development of specialized tissues. To distinguish the underlying mechanisms, in this theoretical work, we investigate the spontaneous emergence of tissue patterns from an ensemble of single cells on a substrate following three leading pathways of cell-cell interactions, namely, direct cell adhesion contacts, matrix mediated mechanical interaction, and chemical signalling. Our analysis shows that the growth kinetics of the aggregation process is distinctly different for each pathway and bears the signature of the specific cell-cell interactions. Interestingly, we find that the average domain size and the mass of the clusters exhibit a power law growth in time under certain interaction mechanisms hitherto unexplored. Further, as observed in experiments, the cluster size distribution can be characterized by stretched exponential functions showing distinct cellular organization processes.


1997 ◽  
Vol 178 (2) ◽  
pp. 132-140 ◽  
Author(s):  
Pedro A Lazo ◽  
Laureano Cuevas ◽  
Ana Gutierrez del Arroyo ◽  
Edurne Orúe

2016 ◽  
Vol 113 (13) ◽  
pp. E1826-E1834 ◽  
Author(s):  
Roni Lehmann-Werman ◽  
Daniel Neiman ◽  
Hai Zemmour ◽  
Joshua Moss ◽  
Judith Magenheim ◽  
...  

Minimally invasive detection of cell death could prove an invaluable resource in many physiologic and pathologic situations. Cell-free circulating DNA (cfDNA) released from dying cells is emerging as a diagnostic tool for monitoring cancer dynamics and graft failure. However, existing methods rely on differences in DNA sequences in source tissues, so that cell death cannot be identified in tissues with a normal genome. We developed a method of detecting tissue-specific cell death in humans based on tissue-specific methylation patterns in cfDNA. We interrogated tissue-specific methylome databases to identify cell type-specific DNA methylation signatures and developed a method to detect these signatures in mixed DNA samples. We isolated cfDNA from plasma or serum of donors, treated the cfDNA with bisulfite, PCR-amplified the cfDNA, and sequenced it to quantify cfDNA carrying the methylation markers of the cell type of interest. Pancreatic β-cell DNA was identified in the circulation of patients with recently diagnosed type-1 diabetes and islet-graft recipients; oligodendrocyte DNA was identified in patients with relapsing multiple sclerosis; neuronal/glial DNA was identified in patients after traumatic brain injury or cardiac arrest; and exocrine pancreas DNA was identified in patients with pancreatic cancer or pancreatitis. This proof-of-concept study demonstrates that the tissue origins of cfDNA and thus the rate of death of specific cell types can be determined in humans. The approach can be adapted to identify cfDNA derived from any cell type in the body, offering a minimally invasive window for diagnosing and monitoring a broad spectrum of human pathologies as well as providing a better understanding of normal tissue dynamics.


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