scholarly journals DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist

2020 ◽  
Author(s):  
Michel Thépaut ◽  
Joanna Luczkowiak ◽  
Corinne Vivès ◽  
Nuria Labiod ◽  
Isabelle Bally ◽  
...  
Keyword(s):  
Innate Immune ◽  
Cell Infection ◽  
Lectin Receptors ◽  
Sign Recognition ◽  
Virus Transfer ◽  
Molecular Events ◽  
Trans Infection ◽  
Direct Cell ◽  
Multiple Interaction ◽  
Antigen Presenting

SummaryThe efficient spread of SARS-CoV-2 resulted in a pandemic that is unique in modern history. Despite early identification of ACE2 as the receptor for viral spike protein, much remains to be understood about the molecular events behind viral dissemination. We evaluated the contribution of C-type lectin receptors (CLRS) of antigen-presenting cells, widely present in air mucosa and lung tissue. DC-SIGN, L-SIGN, Langerin and MGL bind to diverse glycans of the spike using multiple interaction areas. Using pseudovirus and cells derived from monocytes or T-lymphocytes, we demonstrate that while virus capture by the CLRs examined does not allow direct cell infection, DC/L-SIGN, among these receptors, promote virus transfer to permissive ACE2+ cells. A glycomimetic compound designed against DC-SIGN, enable inhibition of this process. Thus, we described a mechanism potentiating viral capture and spreading of infection. Early involvement of APCs opens new avenues for understanding and treating the imbalanced innate immune response observed in COVID-19 pathogenesis

scholarly journals DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist

2021 ◽  
Vol 17 (5) ◽  
pp. e1009576
Author(s):  
Michel Thépaut ◽  
Joanna Luczkowiak ◽  
Corinne Vivès ◽  
Nuria Labiod ◽  
Isabelle Bally ◽  
...  
Keyword(s):  
Cell Infection ◽  
Lectin Receptors ◽  
Viral Dissemination ◽  
Sign Recognition ◽  
Virus Transfer ◽  
Molecular Events ◽  
Trans Infection ◽  
Direct Cell ◽  
Multiple Interaction ◽  
Antigen Presenting

The efficient spread of SARS-CoV-2 resulted in a unique pandemic in modern history. Despite early identification of ACE2 as the receptor for viral spike protein, much remains to be understood about the molecular events behind viral dissemination. We evaluated the contribution of C-type lectin receptors (CLRS) of antigen-presenting cells, widely present in respiratory mucosa and lung tissue. DC-SIGN, L-SIGN, Langerin and MGL bind to diverse glycans of the spike using multiple interaction areas. Using pseudovirus and cells derived from monocytes or T-lymphocytes, we demonstrate that while virus capture by the CLRs examined does not allow direct cell infection, DC/L-SIGN, among these receptors, promote virus transfer to permissive ACE2+ Vero E6 cells. A glycomimetic compound designed against DC-SIGN, enable inhibition of this process. These data have been then confirmed using authentic SARS-CoV-2 virus and human respiratory cell lines. Thus, we described a mechanism potentiating viral spreading of infection.

scholarly journals HIV-1 trans-Infection Mediated by DCs: The Tip of the Iceberg of Cell-to-Cell Viral Transmission

Pathogens ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 39
Author(s):  
Daniel Perez-Zsolt ◽  
Dàlia Raïch-Regué ◽  
Jordana Muñoz-Basagoiti ◽  
Carmen Aguilar-Gurrieri ◽  
Bonaventura Clotet ◽  
...  
Keyword(s):  
Immune Responses ◽  
Ebola Virus ◽  
Viral Transmission ◽  
Productive Infection ◽  
Lectin Receptors ◽  
Enveloped Viruses ◽  
Cellular Targets ◽  
Trans Infection ◽  
Antigen Presenting ◽  
Hiv 1

HIV-1 cell-to-cell transmission is key for an effective viral replication that evades immunity. This highly infectious mechanism is orchestrated by different cellular targets that utilize a wide variety of processes to efficiently transfer HIV-1 particles. Dendritic cells (DCs) are the most potent antigen presenting cells that initiate antiviral immune responses, but are also the cells with highest capacity to transfer HIV-1. This mechanism, known as trans-infection, relies on the capacity of DCs to capture HIV-1 particles via lectin receptors such as the sialic acid-binding I-type lectin Siglec-1/CD169. The discovery of the molecular interaction of Siglec-1 with sialylated lipids exposed on HIV-1 membranes has enlightened how this receptor can bind to several enveloped viruses. The outcome of these interactions can either mount effective immune responses, boost the productive infection of DCs and favour innate sensing, or fuel viral transmission via trans-infection. Here we review these scenarios focusing on HIV-1 and other enveloped viruses such as Ebola virus or SARS-CoV-2.

scholarly journals Nonameric Peptide Orchestrates Signal Transduction in the Activating HLA-E/NKG2C/CD94 Immune Complex as Revealed by All-Atom Simulations

2021 ◽  
Vol 22 (13) ◽  
pp. 6670
Author(s):  
Eva Prašnikar ◽  
Andrej Perdih ◽  
Jure Borišek
Keyword(s):  
Signal Transduction ◽  
Cell Activation ◽  
Nk Cell ◽  
Innate Immune ◽  
Target Cells ◽  
Molecular Events ◽  
Activating Receptors ◽  
Molecular Machinery ◽  
Infected Cells ◽  
Bond Network

The innate immune system’s natural killer (NK) cells exert their cytolytic function against a variety of pathological challenges, including tumors and virally infected cells. Their activation depends on net signaling mediated via inhibitory and activating receptors that interact with specific ligands displayed on the surfaces of target cells. The CD94/NKG2C heterodimer is one of the NK activating receptors and performs its function by interacting with the trimeric ligand comprised of the HLA-E/β2m/nonameric peptide complex. Here, simulations of the all-atom multi-microsecond molecular dynamics in five immune complexes provide atomistic insights into the receptor–ligand molecular recognition, as well as the molecular events that facilitate the NK cell activation. We identify NKG2C, the HLA-Eα2 domain, and the nonameric peptide as the key elements involved in the molecular machinery of signal transduction via an intertwined hydrogen bond network. Overall, the study addresses the complex intricacies that are necessary to understand the mechanisms of the innate immune system.

scholarly journals Susceptibility to Polyomavirus-Induced Tumors in Inbred Mice: Role of Innate Immune Responses

2002 ◽  
Vol 76 (19) ◽  
pp. 9657-9663 ◽  
Author(s):  
Palanivel Velupillai ◽  
John P. Carroll ◽  
Thomas L. Benjamin
Keyword(s):  
Antigen Presenting Cells ◽  
Interleukin 10 ◽  
Cytokine Response ◽  
Innate Immune ◽  
Interleukin 12 ◽  
Cytokine Responses ◽  
Induced Tumors ◽  
Antigen Presenting ◽  
Type 1 Cytokine

ABSTRACT Mice of the PERA/Ei strain (PE mice) are highly susceptible to tumor induction by polyomavirus and transmit their susceptibility in a dominant manner in crosses with resistant C57BR/cdJ mice (BR mice). BR mice respond to polyomavirus infection with a type 1 cytokine response and develop effective cell-mediated immunity to the virus-induced tumors. By enumerating virus-specific CD8+ T cells and measuring cytokine responses, we show that the susceptibility of PE mice is due to the absence of a type 1 cytokine response and a concomitant failure to sustain virus-specific cytotoxic T lymphocytes. (PE × BR)F1 mice showed an initial type 1 response that became skewed toward type 2. Culture supernatants of splenocytes from infected PE mice stimulated in vitro contained high levels of interleukin-10 and no detectable gamma interferon, while those from BR mice showed the opposite pattern. Differences in the innate immune response to polyomavirus by antigen-presenting cells in PE mice and BR mice led to polarization of T-cell cytokine responses. Adherent cells from spleens of infected BR mice produced high levels of interleukin-12, while those from infected PE and F1 mice produced predominantly interleukin-10. PE and F1 mice infected by polyomavirus responded with increases in antigen-presenting cells expressing B7.2 costimulatory molecules, whereas BR mice responded with increased expression of B7.1. Administration of recombinant interleukin-12 along with virus resulted in partial protection of PE mice and provided complete protection against tumor development in F1 animals.

scholarly journals Human coronaviruses 229E and OC43 replicate and induce distinct antiviral responses in differentiated primary human bronchial epithelial cells

2020 ◽  
Vol 319 (6) ◽  
pp. L926-L931
Author(s):  
Su-Ling Loo ◽  
Peter A. B. Wark ◽  
Camille Esneau ◽  
Kristy S. Nichol ◽  
Alan C-Y. Hsu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Time Course ◽  
Bronchial Epithelial Cells ◽  
Innate Immune ◽  
Infection Model ◽  
Type I ◽  
Human Bronchial Epithelial Cells ◽  
Cell Infection ◽  
Bronchial Epithelial ◽  
Human Coronaviruses

The recurrent emergence of novel, pathogenic coronaviruses (CoVs) severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1; 2002), Middle East respiratory syndrome (MERS)-CoV (2012), and most recently SARS-CoV-2 (2019) has highlighted the need for physiologically informative airway epithelial cell infection models for studying immunity to CoVs and development of antiviral therapies. To address this, we developed an in vitro infection model for two human coronaviruses; alphacoronavirus 229E-CoV (229E) and betacoronavirus OC43-CoV (OC43) in differentiated primary human bronchial epithelial cells (pBECs). Primary BECs from healthy subjects were grown at air-liquid interface (ALI) and infected with 229E or OC43, and replication kinetics and time-course expression of innate immune mediators were assessed. OC43 and 229E-CoVs replicated in differentiated pBECs but displayed distinct replication kinetics: 229E replicated rapidly with viral load peaking at 24 h postinfection, while OC43 replication was slower peaking at 96 h after infection. This was associated with diverse antiviral response profiles defined by increased expression of type I/III interferons and interferon-stimulated genes (ISGs) by 229E compared with no innate immune activation with OC43 infection. Understanding the host-virus interaction for previously established coronaviruses will give insight into pathogenic mechanisms underpinning SARS-CoV-2-induced respiratory disease and other future coronaviruses that may arise from zoonotic sources.

scholarly journals MGL Receptor and Immunity: When the Ligand Can Make the Difference

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Ilaria Grazia Zizzari ◽  
Chiara Napoletano ◽  
Federico Battisti ◽  
Hassan Rahimi ◽  
Salvatore Caponnetto ◽  
...  
Keyword(s):  
Immune Response ◽  
Steric Structure ◽  
Activated Macrophages ◽  
Danger Signal ◽  
Lectin Receptors ◽  
Type C ◽  
The Difference ◽  
Antigen Presenting ◽  
Antigen Structure

C-type lectin receptors (CLRs) on antigen-presenting cells (APCs) facilitate uptake of carbohydrate antigens for antigen presentation, modulating the immune response in infection, homeostasis, autoimmunity, allergy, and cancer. In this review, we focus on the role of the macrophage galactose type C-type lectin (MGL) in the immune response against self-antigens, pathogens, and tumor associated antigens (TAA). MGL is a CLR exclusively expressed by dendritic cells (DCs) and activated macrophages (MØs), able to recognize terminal GalNAc residues, including the sialylated and nonsialylated Tn antigens. We discuss the effects on DC function induced throughout the engagement of MGL, highlighting the importance of the antigen structure in the modulation of immune response. Indeed modifying Tn-density, the length, and steric structure of the Tn-antigens can result in generating immunogens that can efficiently bind to MGL, strongly activate DCs, mimic the effects of a danger signal, and achieve an efficient presentation in HLA classes I and II compartments.

scholarly journals Mesenchymal Stromal Cells Affect Disease Outcomes via Macrophage Polarization

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Guoping Zheng ◽  
Menghua Ge ◽  
Guanguan Qiu ◽  
Qiang Shu ◽  
Jianguo Xu
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Spinal Cord Injuries ◽  
Inflammatory Diseases ◽  
Macrophage Polarization ◽  
Cell Contact ◽  
Direct Cell ◽  
Almost All ◽  
Preclinical And Clinical Studies ◽  
Antigen Presenting

Mesenchymal stromal cells (MSCs) are multipotent and self-renewable cells that reside in almost all postnatal tissues. In recent years, many studies have reported the effect of MSCs on the innate and adaptive immune systems. MSCs regulate the proliferation, activation, and effector function of T lymphocytes, professional antigen presenting cells (dendritic cells, macrophages, and B lymphocytes), and NK cells via direct cell-to-cell contact or production of soluble factors including indoleamine 2,3-dioxygenase, prostaglandin E2, tumor necrosis factor-αstimulated gene/protein 6, nitric oxide, and IL-10. MSCs are also able to reprogram macrophages from a proinflammatory M1 phenotype toward an anti-inflammatory M2 phenotype capable of regulating immune response. Because of their capacity for differentiation and immunomodulation, MSCs have been used in many preclinical and clinical studies as possible new therapeutic agents for the treatment of autoimmune, degenerative, and inflammatory diseases. In this review, we discuss the central role of MSCs in macrophage polarization and outcomes of diseases such as wound healing, brain/spinal cord injuries, and diseases of heart, lung, and kidney in animal models.

Molecular events in the processing of avidin by antigen-presenting cells (APC)

1983 ◽  
Vol 18 (3) ◽  
pp. 277-290 ◽  
Author(s):  
Aharon Friedman ◽  
Rachel Zerubavelt ◽  
Carlos Gitler ◽  
Irun R. Cohent
Keyword(s):  
Antigen Presenting Cells ◽  
Molecular Events ◽  
Antigen Presenting
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