scholarly journals Neutrophil and monocyte dysfunctional effector response towards bacterial challenge in critically-ill COVID-19 patients

2020 ◽  
Author(s):  
Srikanth Mairpady Shambat ◽  
Alejandro Gómez-Mejia ◽  
Tiziano A. Schweizer ◽  
Markus Huemer ◽  
Chun-Chi Chang ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Distinct Pattern ◽  
Innate Immune ◽  
Receptor Expression ◽  
Cell Surface Receptor ◽  
Functional Responses ◽  
Innate Immune Signaling ◽  
Surface Receptor ◽  
And Function ◽  
Effector Response

AbstractCOVID-19 displays diverse disease severities and symptoms. Elevated inflammation mediated by hypercytokinemia induces a detrimental dysregulation of immune cells. However, there is limited understanding of how SARS-CoV-2 pathogenesis impedes innate immune signaling and function against secondary bacterial infections. We assessed the influence of COVID-19 hypercytokinemia on the functional responses of neutrophils and monocytes upon bacterial challenges from acute and corresponding recovery COVID-19 ICU patients. We show that severe hypercytokinemia in COVID-19 patients correlated with bacterial superinfections. Neutrophils and monocytes from acute COVID-19 patients showed severely impaired microbicidal capacity, reflected by abrogated ROS and MPO production as well as reduced NETs upon bacterial challenges. We observed a distinct pattern of cell surface receptor expression on both neutrophils and monocytes leading to a suppressive autocrine and paracrine signaling during bacterial challenges. Our data provide insights into the innate immune status of COVID-19 patients mediated by their hypercytokinemia and its transient effect on immune dysregulation upon subsequent bacterial infections

scholarly journals Stimulatory Effects of Peroxisome Proliferator-Activated Receptor-γon FcγReceptor-Mediated Phagocytosis by Alveolar Macrophages

PPAR Research ◽  
2007 ◽  
Vol 2007 ◽  
pp. 1-8 ◽  
Author(s):  
David M. Aronoff ◽  
Carlos H. Serezani ◽  
Jennifer K. Carstens ◽  
Teresa Marshall ◽  
Srinivasa R. Gangireddy ◽  
...  
Keyword(s):  
Alveolar Macrophages ◽  
Peritoneal Macrophages ◽  
Receptor Expression ◽  
Cell Surface Receptor ◽  
Peroxisome Proliferator ◽  
Quiescent State ◽  
Peroxisome Proliferator Activated Receptor ◽  
Downstream Signaling ◽  
Surface Receptor ◽  
And Function

Alveolar macrophages abundantly express PPAR-γ, with both natural and synthetic agonists maintaining the cell in a quiescent state hyporesponsive to antigen stimulation. Conversely, agonists upregulate expression and function of the cell-surface receptor CD36, which mediates phagocytosis of lipids, apoptotic neutrophils, and other unopsonized materials. These effects led us to investigate the actions of PPAR-γagonists on the Fcγreceptor, which mediates phagocytosis of particles opsonized by binding of immunoglobulin G antibodies. We found that troglitazone, rosiglitazone, and 15-deoxy-Δ12,14-prostaglandinJ2increase the ability of alveolar, but not peritoneal, macrophages to carry out phagocytosis mediated by the Fcγreceptor. Receptor expression was not altered but activation of the downstream signaling proteins Syk, ERK-1, and ERK-2 was observed. Although it was previously known that PPAR-γligands stimulate phagocytosis of unopsonized materials, this is the first demonstration that they stimulate phagocytosis of opsonized materials as well.

scholarly journals Hyperinflammatory environment drives dysfunctional myeloid cell effector response to bacterial challenge in COVID-19

2022 ◽  
Vol 18 (1) ◽  
pp. e1010176
Author(s):  
Srikanth Mairpady Shambat ◽  
Alejandro Gómez-Mejia ◽  
Tiziano A. Schweizer ◽  
Markus Huemer ◽  
Chun-Chi Chang ◽  
...  
Keyword(s):  
Acute Phase ◽  
Immune Cells ◽  
Bacterial Infections ◽  
Receptor Expression ◽  
Cell Surface Receptor ◽  
High Expression ◽  
Cytokine Signaling ◽  
Bacterial Challenge ◽  
Functional Responses ◽  
Low Expression

COVID-19 displays diverse disease severities and symptoms including acute systemic inflammation and hypercytokinemia, with subsequent dysregulation of immune cells. Bacterial superinfections in COVID-19 can further complicate the disease course and are associated with increased mortality. However, there is limited understanding of how SARS-CoV-2 pathogenesis and hypercytokinemia impede the innate immune function against bacterial superinfections. We assessed the influence of COVID-19 plasma hypercytokinemia on the functional responses of myeloid immune cells upon bacterial challenges from acute-phase COVID-19 patients and their corresponding recovery (rec)-phase. We show that a severe hypercytokinemia status in COVID-19 patients correlates with the development of bacterial superinfections. Neutrophils and monocytes derived from COVID-19 patients in their acute-phase showed an impaired intracellular microbicidal capacity upon bacterial challenges. The impaired microbicidal capacity was reflected by abrogated MPO and reduced NETs production in neutrophils along with reduced ROS production in both neutrophils and monocytes. Moreover, we observed a distinct pattern of cell surface receptor expression on both neutrophils and monocytes, in line with suppressed autocrine and paracrine cytokine signaling. This phenotype was characterized by a high expression of CD66b, CXCR4 and low expression of CXCR1, CXCR2 and CD15 in neutrophils and low expression of HLA-DR, CD86 and high expression of CD163 and CD11b in monocytes. Furthermore, the impaired antibacterial effector function was mediated by synergistic effect of the cytokines TNF-α, IFN-γ and IL-4. COVID-19 patients receiving dexamethasone showed a significant reduction of overall inflammatory markers in the plasma as well as exhibited an enhanced immune response towards bacterial challenge ex vivo. Finally, broad anti-inflammatory treatment was associated with a reduction in CRP, IL-6 levels as well as length of ICU and hospital stay in critically ill COVID-19 patients. Our data provides insights into the transient functional dysregulation of myeloid immune cells against subsequent bacterial infections in COVID-19 patients and describe a beneficial role for the use of dexamethasone in these patients.

scholarly journals Porcine Breast Extracellular Matrix Hydrogel for Spatial Tissue Culture

2018 ◽  
Vol 19 (10) ◽  
pp. 2912 ◽  
Author(s):  
Girdhari Rijal ◽  
Jing Wang ◽  
Ilhan Yu ◽  
David Gang ◽  
Roland Chen ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Human Mammary Epithelial Cell ◽  
Tumor Formation ◽  
Receptor Expression ◽  
Cell Surface Receptor ◽  
Breast Diseases ◽  
Porous Scaffolds ◽  
Ecm Proteins ◽  
Surface Receptor

Porcine mammary fatty tissues represent an abundant source of natural biomaterial for generation of breast-specific extracellular matrix (ECM). Here we report the extraction of total ECM proteins from pig breast fatty tissues, the fabrication of hydrogel and porous scaffolds from the extracted ECM proteins, the structural properties of the scaffolds (tissue matrix scaffold, TMS), and the applications of the hydrogel in human mammary epithelial cell spatial cultures for cell surface receptor expression, metabolomics characterization, acini formation, proliferation, migration between different scaffolding compartments, and in vivo tumor formation. This model system provides an additional option for studying human breast diseases such as breast cancer.

scholarly journals Drebrin 1 in dendritic cells regulates phagocytosis and cell surface receptor expression through recycling for efficient antigen presentation

Immunology ◽  
2018 ◽  
Vol 156 (2) ◽  
pp. 136-146 ◽  
Author(s):  
Diana M. Elizondo ◽  
Temesgen E. Andargie ◽  
Naomi L. Haddock ◽  
Thomas A. Boddie ◽  
Michael W. Lipscomb
Keyword(s):  
Dendritic Cells ◽  
Cell Surface ◽  
Antigen Presentation ◽  
Receptor Expression ◽  
Cell Surface Receptor ◽  
Surface Receptor

scholarly journals Correlated STORM-homoFRET Imaging: Applications to the Study of Membrane Receptor Self-Association and Clustering

2021 ◽  
Author(s):  
Amine Driouchi ◽  
Scott Gray-Owen ◽  
Christopher M Yip
Keyword(s):  
Spatial Distribution ◽  
Membrane Proteins ◽  
Complex Mixture ◽  
Cell Surface Receptor ◽  
Oligomeric State ◽  
Imaging Approach ◽  
Surface Receptor ◽  
A Cell ◽  
Self Association ◽  
And Function

Mapping the self-organization and spatial distribution of membrane proteins is key to understanding their function. We report here on a correlated STORM/homoFRET imaging approach for resolving the nanoscale distribution and oligomeric state of membrane proteins. Live cell homoFRET imaging of CEACAM1, a cell-surface receptor known to exist in a complex equilibrium between monomer and dimer/oligomer states, revealed highly heterogenous diffraction-limited structures on the surface of HeLa cells. Correlated super-resolved STORM imaging revealed that these structures comprised a complex mixture and spatial distribution of self-associated CEACAM1 molecules. This correlated approach provides a compelling strategy for addressing challenging questions about the interplay between membrane protein concentration, distribution, interaction, clustering, and function.

scholarly journals Selective inhibition of the growth of human erythroid bursts by monoclonal antibodies against transferrin or the transferrin receptor

Blood ◽  
1986 ◽  
Vol 67 (6) ◽  
pp. 1631-1638 ◽  
Author(s):  
KM Shannon ◽  
JW Larrick ◽  
SA Fulcher ◽  
KB Burck ◽  
J Pacely ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Transferrin Receptor ◽  
Thymidine Incorporation ◽  
Selective Inhibition ◽  
Receptor Expression ◽  
Cell Surface Receptor ◽  
Transferrin Receptors ◽  
Human Erythropoietin ◽  
Surface Receptor ◽  
Transferrin Receptor Expression

Abstract The relative requirements of colonies derived from erythroid (BFU-E) and myeloid (CFU-c) progenitors for transferrin were examined using monoclonal antibodies directed against the transferrin molecule (TF-6) or its cell surface receptor (TFR-A12, TFR1–2B). Growth of erythroid bursts was profoundly reduced at concentrations of all three antibodies that had no effect on CFU-c-derived colonies. When TFR1–2B was layered over cultures established one to seven days previously, further burst development was inhibited, and degeneration of early erythroid colonies was observed. Addition of erythropoietin augmented transferrin receptor expression on cells harvested after 1 to 2 weeks in culture and analyzed by flow cytometry. Recombinant human erythropoietin gave results comparable to those obtained in experiments using human urinary erythropoietin. Analysis of erythroblasts plucked directly from culture plates confirmed the presence of transferrin receptors on BFU-E-derived colonies. Thymidine incorporation was maximal early in the second week of culture and coincided with high transferrin receptor expression. These data demonstrate that transferrin must be available into the second week of culture to support the growth and differentiation of BFU- E-derived erythroid bursts, that the generation of erythroid colonies from BFU-E is more dependent on transferrin than myeloid colony formation from CFU-c, and that erythropoietin modulates the expression of transferrin receptors on growing bursts.

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