Morphotype-specific effector functions of Cryptococcus neoformans PUM1

Abstract In COVID-19, immune responses are key in determining disease severity. However, cellular mechanisms at the onset of inflammatory lung injury in SARS-CoV-2 infection, particularly involving endothelial cells, remain ill-defined. Using Syrian hamsters as model for moderate COVID-19, we conducted a detailed longitudinal analysis of systemic and pulmonary cellular responses, and corroborated it with datasets from COVID-19 patients. Monocyte-derived macrophages in lungs exerted the earliest and strongest transcriptional response to infection, including induction of pro-inflammatory genes, while epithelial cells showed weak activation. Without evidence for productive infection, endothelial cells reacted, depending on cell subtypes, by strong and early expression of anti-viral, pro-inflammatory, and T cell recruiting genes. Recruitment of cytotoxic T cells as well as emergence of IgM antibodies preceded viral clearance at day 5 post infection. Investigating SARS-CoV-2 infected Syrian hamsters can thus identify cell type-specific effector functions, provide detailed insights into pathomechanisms of COVID-19, and inform therapeutic strategies.

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CARs: Beyond T Cells and T Cell-Derived Signaling Domains

International Journal of Molecular Sciences ◽

10.3390/ijms21103525 ◽

2020 ◽

Vol 21 (10) ◽

pp. 3525 ◽

Cited By ~ 4

Author(s):

Nico M. Sievers ◽

Jan Dörrie ◽

Niels Schaft

Keyword(s):

Cell Types ◽

Antigen Binding ◽

Cell Type ◽

Transfected Cells ◽

Effector Functions ◽

Binding Domains ◽

Specific Effector ◽

Different Cell Types ◽

Intracellular Domains ◽

Signaling Domains

When optimizing chimeric antigen receptor (CAR) therapy in terms of efficacy, safety, and broadening its application to new malignancies, there are two main clusters of topics to be addressed: the CAR design and the choice of transfected cells. The former focuses on the CAR construct itself. The utilized transmembrane and intracellular domains determine the signaling pathways induced by antigen binding and thereby the cell-specific effector functions triggered. The main part of this review summarizes our understanding of common signaling domains employed in CARs, their interactions among another, and their effects on different cell types. It will, moreover, highlight several less common extracellular and intracellular domains that might permit unique new opportunities. Different antibody-based extracellular antigen-binding domains have been pursued and optimized to strike a balance between specificity, affinity, and toxicity, but these have been reviewed elsewhere. The second cluster of topics is about the cellular vessels expressing the CAR. It is essential to understand the specific attributes of each cell type influencing anti-tumor efficacy, persistence, and safety, and how CAR cells crosstalk with each other and bystander cells. The first part of this review focuses on the progress achieved in adopting different leukocytes for CAR therapy.

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Search for Specific Effector Functions of C3H × CBA Lymphocytes which Have Proliferated in the Spleens of Irradiated CBA Mice

International Archives of Allergy and Immunology ◽

10.1159/000232358 ◽

1979 ◽

Vol 60 (3) ◽

pp. 325-331

Author(s):

Bo Lilliehöök ◽

Henric Blomgren

Keyword(s):

Effector Functions ◽

Cba Mice ◽

Specific Effector

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Human Monoclonal Antibodies to Glycolipid A that Exhibit Complement Species-Specific Effector Functions

The Journal of Infectious Diseases ◽

10.1093/infdis/165.1.26 ◽

1992 ◽

Vol 165 (1) ◽

pp. 26-33 ◽

Cited By ~ 6

Author(s):

J. L. Winkelhake ◽

S. S. Gauny ◽

G. Senyk ◽

D. Piazza ◽

P. Stevens

Keyword(s):

Monoclonal Antibodies ◽

Human Monoclonal Antibodies ◽

Effector Functions ◽

Specific Effector ◽

Species Specific

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Abstract 895: Coexpression of MHC class I-restricted neoTCRs and ectopic CD8 receptors in precision genome engineered CD4 T cells significantly potentiates antigen-specific effector functions

10.1158/1538-7445.am2020-895 ◽

2020 ◽

Author(s):

Barbara Sennino ◽

Andrew Conroy ◽

Bhamini Purandare ◽

Kyle Jacoby ◽

Olivier Dalmas ◽

...

Keyword(s):

T Cells ◽

Mhc Class I ◽

Cd4 T Cells ◽

Class I ◽

Effector Functions ◽

Specific Effector

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Temporal omics analysis in Syrian hamsters unravel cellular effector responses to moderate COVID-19

Nature Communications ◽

10.1038/s41467-021-25030-7 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Geraldine Nouailles ◽

Emanuel Wyler ◽

Peter Pennitz ◽

Dylan Postmus ◽

Daria Vladimirova ◽

...

Keyword(s):

Endothelial Cells ◽

Cytotoxic T Cells ◽

Transcriptional Response ◽

Productive Infection ◽

Cellular Mechanisms ◽

Syrian Hamsters ◽

Effector Functions ◽

Specific Effector ◽

Early Expression ◽

Cell Type Specific

AbstractIn COVID-19, immune responses are key in determining disease severity. However, cellular mechanisms at the onset of inflammatory lung injury in SARS-CoV-2 infection, particularly involving endothelial cells, remain ill-defined. Using Syrian hamsters as a model for moderate COVID-19, we conduct a detailed longitudinal analysis of systemic and pulmonary cellular responses, and corroborate it with datasets from COVID-19 patients. Monocyte-derived macrophages in lungs exert the earliest and strongest transcriptional response to infection, including induction of pro-inflammatory genes, while epithelial cells show weak alterations. Without evidence for productive infection, endothelial cells react, depending on cell subtypes, by strong and early expression of anti-viral, pro-inflammatory, and T cell recruiting genes. Recruitment of cytotoxic T cells as well as emergence of IgM antibodies precede viral clearance at day 5 post infection. Investigating SARS-CoV-2 infected Syrian hamsters thus identifies cell type-specific effector functions, providing detailed insights into pathomechanisms of COVID-19 and informing therapeutic strategies.

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Human Immunoglobulin G2 (IgG2) and IgG4, but Not IgG1 or IgG3, Protect Mice against Cryptococcus neoformans Infection

Infection and Immunity ◽

10.1128/iai.01161-06 ◽

2007 ◽

Vol 75 (3) ◽

pp. 1424-1435 ◽

Cited By ~ 52

Author(s):

David O. Beenhouwer ◽

Esther M. Yoo ◽

Chun-Wei Lai ◽

Miguel A. Rocha ◽

Sherie L. Morrison

Keyword(s):

Cryptococcus Neoformans ◽

Capsular Polysaccharide ◽

Human Immunoglobulin ◽

Variable Regions ◽

Effector Functions ◽

Antibody Therapeutics ◽

Human Igg1 ◽

Effector Pathways ◽

Phosphate Buffered Saline ◽

Murine Monoclonal Antibodies

ABSTRACT The encapsulated yeast Cryptococcus neoformans is a significant cause of meningitis and death in patients with AIDS. Some murine monoclonal antibodies (MAbs) against the glucuronoxylomannan (GXM) component of the C. neoformans capsular polysaccharide can prolong the lives of infected mice, while others have no effect or can even shorten survival. To date, no one has systematically compared the efficacies of antibodies with the same variable regions and different human constant regions with their unique combination of effector functions in providing protection against murine C. neoformans infection. In the present study, we examined the efficacies of anti-GXM MAbs of the four human immunoglobulin G (IgG) subclasses, which have identical variable regions but differ in their capacities to bind the three types of Fc receptors for IgG (FcγR), their abilities to activate complement, and their half-lives. IgG2 and IgG4 anti-GXM prolonged the lives of infected BALB/c mice, IgG3 anti-GXM did not affect animal survival, while mice treated with IgG1 anti-GXM died earlier than mice treated with phosphate-buffered saline or irrelevant isotype-matched MAbs. All MAbs decreased serum GXM in infected animals. Effector pathways traditionally believed to be important in defense against microbes, such as opsonophagocytosis and complement binding, negatively correlated with antibody efficacy. It is generally accepted that human IgG1 has the most favorable combination of effector functions for therapeutic use against infections. Therefore, our findings have significant implications for humanization of the mouse IgG1 currently in clinical trials for cryptococcal meningitis and for the design of antibody therapeutics to treat other infectious diseases as well.

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