scholarly journals Single cell RNA sequencing of blood antigen-presenting cells in severe Covid-19 reveals multi-process defects in antiviral immunity

2020 ◽  
Author(s):  
Melissa Saichi ◽  
Maha Zohra Ladjemi ◽  
Sarantis Korniotis ◽  
Christophe Rousseau ◽  
Zakaria Ait-Hamou ◽  
...  
Keyword(s):  
Single Cell ◽  
Rna Sequencing ◽  
Mhc Class Ii ◽  
Antigen Presenting Cells ◽  
Antiviral Immunity ◽  
Class Ii ◽  
Immune Defense ◽  
Simultaneous Increase ◽  
Single Cell Rna Sequencing ◽  
Antigen Presenting

AbstractCOVID-19 can lead to life-threatening acute respiratory failure, characterized by simultaneous increase in inflammatory mediators and viral load. The underlying cellular and molecular mechanisms remain unclear. We performed single-cell RNA-sequencing to establish an exhaustive high-resolution map of blood antigen-presenting cells (APC) in 7 COVID-19 patients with moderate or severe pneumonia, at day-1 and day-4 post-admission, and two healthy donors. We generated a unique dataset of 31,513 high quality APC, including monocytes and rare dendritic cell (DC) subsets. We uncovered multiprocess and previously unrecognized defects in anti-viral immune defense in specific APC compartments from severe patients: i) increase of pro-apoptotic genes exclusively in pDC, which are key effectors of antiviral immunity, ii) sharp decrease of innate sensing receptors, TLR7 and DHX9, in pDC and cDC1, respectively, iii) down-regulation of antiviral effector molecules, including Interferon stimulated genes (ISG) in all monocyte subsets, and iv) decrease of MHC class II-related genes, and MHC class II transactivator (CIITA) activity in cDC2, suggesting a viral inhibition of antigen presentation. These novel mechanisms may explain patient aggravation and suggest strategies to restore defective immune defense.

scholarly journals Single-cell RNA sequencing of blood antigen-presenting cells in severe COVID-19 reveals multi-process defects in antiviral immunity

2021 ◽  
Author(s):  
Melissa Saichi ◽  
Maha Zohra Ladjemi ◽  
Sarantis Korniotis ◽  
Christophe Rousseau ◽  
Zakaria Ait Hamou ◽  
...  
Keyword(s):  
Single Cell ◽  
Rna Sequencing ◽  
Antigen Presenting Cells ◽  
Antiviral Immunity ◽  
Single Cell Rna Sequencing ◽  
Antigen Presenting

Allotransplantation of culture-isolated neonatal rat islet tissue. Absence of MHC class II positive antigen-presenting cells in nonimmunogenic islets

Diabetes ◽  
1989 ◽  
Vol 38 (2) ◽  
pp. 146-151 ◽  
Author(s):  
O. D. Hegre ◽  
R. J. Ketchum ◽  
H. Popiela ◽  
C. R. Eide ◽  
R. M. Meloche ◽  
...  
Keyword(s):  
Mhc Class Ii ◽  
Antigen Presenting Cells ◽  
Class Ii ◽  
Neonatal Rat ◽  
Islet Tissue ◽  
Antigen Presenting

scholarly journals Stratification of Antigen-presenting Cells within the Normal Cornea

2009 ◽  
Vol 1 ◽  
pp. OED.S2813 ◽  
Author(s):  
Jared E. Knickelbein ◽  
Simon C. Watkins ◽  
Paul G. Mcmenamin ◽  
Robert L. Hendricks
Keyword(s):  
Bone Marrow ◽  
Basement Membrane ◽  
Mhc Class Ii ◽  
Fluorescent Protein ◽  
Antigen Presenting Cells ◽  
Class Ii ◽  
Apical Surface ◽  
Bone Marrow Derived Cells ◽  
Green Fluorescent ◽  
Antigen Presenting

The composition and location of professional antigen presenting cells (APC) varies in different mucosal surfaces. The cornea, long considered an immune-privileged tissue devoid of APCs, is now known to host a heterogeneous network of bone marrow-derived cells. Here, we utilized transgenic mice that express enhanced green fluorescent protein (EGFP) from the CD 11c promoter (pCD11c) in conjunction with immunohistochemical staining to demonstrate an interesting stratification of APCs within non-inflamed murine corneas. pCD11c+ dendritic cells (DCs) reside in the basal epithelium, seemingly embedded in the basement membrane. Most DCs express MHC class II on at least some dendrites, which extend up to 50 μm in length and traverse up 20 μm tangentially towards the apical surface of the epithelium. The DC density diminishes from peripheral to central cornea. Beneath the DCs and adjacent to the stromal side of the basement membrane reside pCD11c–CD11b+ putative macrophages that express low levels of MHC class II. Finally, MHC class II–pCD11c–CD11b+ cells form a network throughout the remainder of the stroma. This highly reproducible stratification of bone marrow-derived cells is suggestive of a progression from an APC function at the exposed corneal surface to an innate immune barrier function deeper in the stroma.

Endocytosis and Biosynthetic Transport of Murine MHC Class II Molecules in Antigen Presenting Cells

Endocytosis ◽  
1992 ◽  
pp. 341-342
Author(s):  
J. Davoust ◽  
P. Cosson ◽  
J. M. Escola ◽  
J. Henry ◽  
M. Humbert ◽  
...  
Keyword(s):  
Mhc Class Ii ◽  
Antigen Presenting Cells ◽  
Class Ii ◽  
Antigen Presenting ◽  
Mhc Class Ii Molecules

scholarly journals Single-Cell Transcriptomic Analysis of Tumor-Derived Fibroblasts and Normal Tissue-Resident Fibroblasts Reveals Fibroblast Heterogeneity in Breast Cancer

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1307 ◽  
Author(s):  
Aimy Sebastian ◽  
Nicholas R. Hum ◽  
Kelly A. Martin ◽  
Sean F. Gilmore ◽  
Ivana Peran ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Single Cell ◽  
Mhc Class Ii ◽  
Smooth Muscle Actin ◽  
Class Ii ◽  
Normal Breast ◽  
Syngeneic Mouse Model ◽  
Elevated Expression ◽  
Tumor Types ◽  
Antigen Presenting

Cancer-associated fibroblasts (CAFs) are a prominent stromal cell type in solid tumors and molecules secreted by CAFs play an important role in tumor progression and metastasis. CAFs coexist as heterogeneous populations with potentially different biological functions. Although CAFs are a major component of the breast cancer stroma, molecular and phenotypic heterogeneity of CAFs in breast cancer is poorly understood. In this study, we investigated CAF heterogeneity in triple-negative breast cancer (TNBC) using a syngeneic mouse model, BALB/c-derived 4T1 mammary tumors. Using single-cell RNA sequencing (scRNA-seq), we identified six CAF subpopulations in 4T1 tumors including: 1) myofibroblastic CAFs, enriched for α-smooth muscle actin and several other contractile proteins; 2) ‘inflammatory’ CAFs with elevated expression of inflammatory cytokines; and 3) a CAF subpopulation expressing major histocompatibility complex (MHC) class II proteins that are generally expressed in antigen-presenting cells. Comparison of 4T1-derived CAFs to CAFs from pancreatic cancer revealed that these three CAF subpopulations exist in both tumor types. Interestingly, cells with inflammatory and MHC class II-expressing CAF profiles were also detected in normal breast/pancreas tissue, suggesting that these phenotypes are not tumor microenvironment-induced. This work enhances our understanding of CAF heterogeneity, and specifically targeting these CAF subpopulations could be an effective therapeutic approach for treating highly aggressive TNBCs.

Allotransplantation of Culture-Isolated Neonatal Rat Islet Tissue: Absence of MHC Class II Positive Antigen-Presenting Cells in Nonimmunogenic Islets

Diabetes ◽  
1989 ◽  
Vol 38 (2) ◽  
pp. 146-151 ◽  
Author(s):  
O. D. Hegre ◽  
R. J. Ketchum ◽  
H. Popiela ◽  
C. R. Eide ◽  
R. M. Meloche ◽  
...  
Keyword(s):  
Mhc Class Ii ◽  
Antigen Presenting Cells ◽  
Class Ii ◽  
Neonatal Rat ◽  
Islet Tissue ◽  
Antigen Presenting

scholarly journals Quantitative Analysis of the Efficiency of Clonal Deletion in the Thymus

1994 ◽  
Vol 4 (1) ◽  
pp. 43-53 ◽  
Author(s):  
Lisa M. Spain ◽  
Leslie J. Berg
Keyword(s):  
Epithelial Cells ◽  
Mhc Class Ii ◽  
Negative Selection ◽  
Gene Dosage ◽  
Antigen Presenting Cells ◽  
Class Ii ◽  
Clonal Deletion ◽  
Self Tolerance ◽  
Antigen Presenting ◽  
Mhc Class Ii Molecules

One of the major mechanisms for establishing self-tolerance is the clonal deletion of self-reactive T cells during their development in the thymus. Using a TCR transgenic mouse model, we have established a quantitativeex vivoassay for examining the sensitivity and specificity of negative selection. Thymic organ cultures established from mice of varying MHC haplotypes were incubated with antigen, and the efficiency of clonal deletion assessed. We show here that clonal deletion of CD4+8+thymocytes is sensitive to both the gene dosage and the allelic variation of MHC class II molecules expressed on thymic antigen-presenting cells. We also find that when epithelial cells in the thymic cortex are the only antigen-presenting cells expressing the appropriate MHC class II molecules, negative selection of CD4+8+cells is as efficient as when antigen is presented on all thymic antigen-presenting cells. These studies demonstrate that the induction of self-tolerance via clonal deletion in the thymus is a function not only of antigen concentration, but also of MHC class II cell-surface density. In addition, together with the reports of others, these results confirm that cortical epithelial cells can mediate negative selection, and demonstrate that they do so in the intact thymic microenvironment.

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