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Myeloid CD169/Siglec1: An immunoregulatory biomarker in viral disease

FRONTIERS IN MEDICINE (2022)

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Altered increase in STAT1 expression and phosphorylation in severe COVID-19

Hector Rincon-Arevalo et al.

Summary: Investigating the interferon signaling pathway in immune cells of COVID-19 patients revealed an upregulation of STAT1 and IRF9 in both mild and severe cases, as well as enhanced phosphorylation of STAT1 in severe cases. This dysbalanced JAK/STAT signaling may lead to insufficient transcription of interferon stimulated response elements (ISRE), suggesting a potential predictive biomarker for targeted interferon pathway treatments.

EUROPEAN JOURNAL OF IMMUNOLOGY (2022)

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Article Allergy

Upregulation of type 1 conventional dendritic cells implicates antigen cross-presentation in multisystem inflammatory syndrome

Janice J. Huang et al.

Summary: This study aimed to analyze the immunologic features of MIS-C patients compared to febrile controls. The results showed that elevated cytokines, activation of type 1 dendritic cells, and dysregulation of NK cells were key features in the pathophysiology of this syndrome.

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY (2022)

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Article Multidisciplinary Sciences

CD169+macrophages in lymph node and spleen critically depend on dual RANK and LTbetaR signaling

Abdouramane Camara et al.

Summary: CD169+ macrophages in lymph nodes and spleen require dual signals from LT beta R and RANK for their differentiation. RANKL is necessary for the formation of their niche in lymph nodes, while splenic marginal zone stromal cells provide the source of RANKL for marginal metallophilic macrophage differentiation in the spleen. Loss of these macrophages compromises viral capture and the expansion of virus-specific CD8+ T cells.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2022)

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Review Microbiology

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

Daniel Perez-Zsolt et al.

Summary: Cell-to-cell transmission of HIV-1 is a highly infectious mechanism that utilizes dendritic cells and lectin receptor Siglec-1 to transfer viral particles. This mechanism can induce immune responses, enhance cellular infection, or promote innate sensing, leading to viral transmission.

PATHOGENS (2022)

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Article Immunology

A Microbiota-Dependent Subset of Skin Macrophages Protects Against Cutaneous Bacterial Infection

Young Joon Park et al.

Summary: This article examines the impact of the microbiota on the skin immune system, revealing the essential role of CD169(+) macrophages in combating bacterial skin infections.

FRONTIERS IN IMMUNOLOGY (2022)

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Article Biochemical Research Methods

CD169 and CD64 could help differentiate bacterial from CoVID-19 or other viral infections in the Emergency Department

Penelope Bourgoin et al.

Summary: The study found that nCD64 and mCD169 can effectively distinguish bacterial infections and acute viral infections, potentially improving infection management in the ED and aiding in patient triage during emerging epidemics.

CYTOMETRY PART A (2021)

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Letter Immunology

SARS-CoV-2 interaction with Siglec-1 mediates trans-infection by dendritic cells

Daniel Perez-Zsolt et al.

CELLULAR & MOLECULAR IMMUNOLOGY (2021)

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Article Chemistry, Multidisciplinary

Liposome induction of CD8+ T cell responses depends on CD169+ macrophages and Batf3-dependent dendritic cells and is enhanced by GM3 inclusion

J. Grabowska et al.

Summary: In this study, liposomes containing GM3 were shown to efficiently target CD169(+) macrophages, inducing specific immune responses including antigen-specific CD8(+) and CD4(+) T cell as well as B cell responses. Administration of GM3 liposomes containing ovalbumin resulted in delayed tumor growth and improved survival in B16-OVA tumor bearing mice. The study also highlighted the essential role of CD169(+) macrophages and cDC1s in inducing CD8(+) T cell immunity through liposomal vaccination.

JOURNAL OF CONTROLLED RELEASE (2021)

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Article Immunology

Monocyte CD169 Expression as a Biomarker in the Early Diagnosis of Coronavirus Disease 2019

Anne-Sophie Bedin et al.

Summary: Monocyte CD169 was significantly overexpressed in confirmed COVID-19 cases, associated with plasma interferon-alpha level and thrombocytopenia, suggesting that testing may aid in rapid triage of suspected COVID-19 patients during an outbreak.

JOURNAL OF INFECTIOUS DISEASES (2021)

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Article Cell Biology

Dissemination of Mycobacterium tuberculosis is associated to a SIGLEC1 null variant that limits antigen exchange via trafficking extracellular vesicles

Susana Benet et al.

Summary: The SIGLEC1 null variant is significantly associated with extrapulmonary dissemination of Mycobacterium tuberculosis, potentially leading to delayed immunity and local bacterial spread. Lack of Siglec-1 limits antigen exchange, increasing the risk of extrapulmonary dissemination.

JOURNAL OF EXTRACELLULAR VESICLES (2021)

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Article Immunology

Liposomal Nanovaccine Containing α-Galactosylceramide and Ganglioside GM3 Stimulates Robust CD8+ T Cell Responses via CD169+ Macrophages and cDC1

Joanna Grabowska et al.

Summary: Successful anti-cancer vaccines targeting cytotoxic T cells and immune cell interactions through GM3-alpha GC-OVA liposomes show promising results in inducing strong adaptive immunity against cancer. The activation of CD8(+) T cells, NKT, and NK cells plays a critical role in the potent immune response, highlighting the potential of this vaccine platform for anti-cancer strategies.

VACCINES (2021)

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Article Biochemical Research Methods

Monocyte CD169 expression in COVID-19 patients upon intensive care unit admission

Marine Ortillon et al.

Summary: The expression of CD169 was substantially increased on monocytes of COVID-19 patients compared to healthy individuals and those with bacterial sepsis. CD169 testing in the ICU may aid in rapidly identifying COVID-19 etiology in patients with acute respiratory failure.

CYTOMETRY PART A (2021)

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Article Infectious Diseases

CD169/SIGLEC1 is expressed on circulating monocytes in COVID-19 and expression levels are associated with disease severity

Jan-Moritz Doehn et al.

Summary: In patients with COVID-19, higher monocytic CD169/SIGLEC1 expression levels were found in those with mild disease compared to severe cases. Further clinical studies are recommended to evaluate the value of CD169/SIGLEC1 expression in patients with COVID-19 with or without auto-antibodies against type I interferons.

INFECTION (2021)

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Article Microbiology

High CD169 Monocyte/Lymphocyte Ratio Reflects Immunophenotype Disruption and Oxygen Need in COVID-19 Patients

Antonella Minutolo et al.

Summary: CD169 is found to be overexpressed in the blood of COVID-19 patients, and is identified as a biomarker. The high CD169 RMFI in COVID-19 patients is associated with CD8 T-cell senescence and exhaustion markers, as well as with B-cell maturation and differentiation. CD169 is induced by the spike protein of SARS-CoV-2 and can be considered as an early biomarker for evaluating immune dysfunction and respiratory outcomes in COVID-19 patients.

PATHOGENS (2021)

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Review Biology

Siglecs as Therapeutic Targets in Cancer

Jackwee Lim et al.

Summary: Hyperglycosylated cancer cells utilize hyper sialic acid expression to manipulate the immune system, leading to immune suppression and tumor growth. Targeting Siglec-sialic acid interactions through strategies like antibodies and glycan moieties can enhance anti-tumor immune responses and improve cancer immunotherapy outcomes.

BIOLOGY-BASEL (2021)

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Article Cell Biology

CD169+ lymph node macrophages have protective functions in mouse breast cancer metastasis

Carlotta Tacconi et al.

Summary: This study shows that CD169(+) lymph node macrophages play a protective role in breast cancer metastasis, and their expansion is linked to B cell expansion in tumor-draining lymph nodes. Depletion of these macrophages increases metastatic burden, highlighting the caution needed in targeting tumor-associated macrophages to avoid unintended consequences in tumor-draining lymph nodes.

CELL REPORTS (2021)

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Article Medicine, General & Internal

Validation of a Quick Flow Cytometry-Based Assay for Acute Infection Based on CD64 and CD169 Expression. New Tools for Early Diagnosis in COVID-19 Pandemic

Alejandra Comins-Boo et al.

Summary: The study confirms that CD64N and CD169Mo ratios can serve as biomarkers for acute bacterial and viral infections, with the potential for quick pathogen identification and direct therapy - particularly beneficial during the COVID-19 pandemic.

FRONTIERS IN MEDICINE (2021)

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Article Multidisciplinary Sciences

Lectins enhance SARS-CoV-2 infection and influence neutralizing antibodies

Florian A. Lempp et al.

Summary: The study reveals that C-type lectin receptors and other factors can serve as attachment receptors for SARS-CoV-2 infection, enhancing ACE2-mediated infection and modulating the neutralizing activity of antibodies.

NATURE (2021)

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Article Biology

In vivo imaging of retrovirus infection reveals a role for Siglec-1/CD169 in multiple routes of transmission

Kelsey A. Haugh et al.

Summary: Using bioluminescence imaging, the study demonstrated how retroviruses exploit the immune surveillance function of tissue-resident sentinel macrophages mediated by the I-type lectin CD169 to establish infection through lymph, blood, and milk transmission routes.

ELIFE (2021)

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Article Immunology

CD169 Defines Activated CD14+ Monocytes With Enhanced CD8+ T Cell Activation Capacity

Alsya J. Affandi et al.

Summary: CD169(+) monocytes are activated monocytes with enhanced capacity to stimulate CD8(+) T cells. They are present in various diseases, including viral infections and cancers, and emerge as an interesting target in nanovaccine strategies. The study also showed that two CD169-targeting nanovaccine platforms efficiently presented tumor-associated peptides to antigen-specific CD8(+) T cells.

FRONTIERS IN IMMUNOLOGY (2021)

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Article Microbiology

CyTOF Profiling of Zika and Dengue Virus-Infected Human Peripheral Blood Mononuclear Cells Identifies Phenotypic Signatures of Monotype Subsets and Upregulation of the Interferon-Inducible Protein CD169

Rafael Fenutria et al.

Summary: This study used mass cytometry to analyze the innate immune responses induced by Zika virus and dengue virus in human PBMCs, revealing that both viruses caused global phenotypic changes in myeloid cells and an expansion of non-classical monocytes. Analysis at the single-cell level identified differences in expression of specific molecules during infection with Zika virus and dengue virus.

MSPHERE (2021)

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Article Cell Biology

Comparative immune profiling of acute respiratory distress syndrome patients with or without SARS-CoV-2 infection

Mikael Roussel et al.

Summary: Researchers found that COVID-19-associated ARDS patients have a specific immune profile that differs from other ARDS patients. Severe COVID-19 patients, regardless of whether they have ARDS or not, display similar immune profiles.

CELL REPORTS MEDICINE (2021)

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Article Microbiology

Flow cytometry evaluation of infection-related biomarkers in febrile subjects in the emergency department

Penelope Bourgoin et al.

FUTURE MICROBIOLOGY (2020)

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Review Immunology

Physiology of gangliosides and the role of antiganglioside antibodies in human diseases

Gianni Cutillo et al.

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Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients

Jerome Hadjadj et al.

SCIENCE (2020)

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Article Rheumatology

SIGLEC1 (CD169) is a sensitive biomarker for the deterioration of the clinical course in childhood systemic lupus erythematosus

Sae Lim von Stuckrad et al.

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A Longitudinal Study of Immune Cells in Severe COVID-19 Patients

Didier Payen et al.

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Optimization of Liposomes for Antigen Targeting to Splenic CD169+ Macrophages

Maarten K. Nijen Twilhaar et al.

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Role of the interferons in CD64 and CD169 expressions in whole blood: Relevance in the balance between viral- or bacterial-oriented immune responses

Penelope Bourgoin et al.

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Lymph Node Mesenchymal and Endothelial Stromal Cells Cooperate via the RANK-RANKL Cytokine Axis to Shape the Sinusoidal Macrophage Niche

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Siglecs: A journey through the evolution of sialic acid-binding immunoglobulin-type lectins

Kim F. Bornhoefft et al.

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Siglec-1 inhibits RSV-induced interferon gamma production by adult Tcells in contrast to newborn Tcells

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Functional CD169 on Macrophages Mediates Interaction with Dendritic Cells for CD8(+) T Cell Cross-Priming

Dieke van Dinther et al.

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CD169+ Macrophages Capture and Dendritic Cells Instruct: The Interplay of the Gatekeeper and the General of the Immune System

Joanna Grabowska et al.

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Retroviruses As Myeloid Cell Riders: What Natural Human Siglec-1 Knockouts Tell Us About Pathogenesis

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SIGLEC1 is a biomarker of disease activity and indicates extraglandular manifestation in primary Sjogren's syndrome

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HIV-1 immune activation induces Siglec-1 expression and enhances viral trans-infection in blood and tissue myeloid cells

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Retroviruses use CD169-mediated trans-infection of permissive lymphocytes to establish infection

Xaver Sewald et al.

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CD169-Mediated Trafficking of HIV to Plasma Membrane Invaginations in Dendritic Cells Attenuates Efficacy of Anti-gp120 Broadly Neutralizing Antibodies

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CD169-Dependent Cell-Associated HIV-1 Transmission: A Driver of Virus Dissemination

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An Intact Sialoadhesin (Sn/SIGLEC1/CD169) Is Not Required for Attachment/Internalization of the Porcine Reproductive and Respiratory Syndrome Virus

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Increased Monocyte Expression of Sialoadhesin During Acute Cellular Rejection and Other Enteritides After Intestine Transplantation in Children

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CD169+ macrophages present lipid antigens to mediate early activation of iNKT cells in lymph nodes

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Sialoadhesin and CD163 join forces during entry of the porcine reproductive and respiratory syndrome virus

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Sialoadhesin Expressed on IFN-Induced Monocytes Binds HIV-1 and Enhances Infectivity

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Sialoadhesin (CD169) Expression in CD14+Cells Is Upregulated Early after HIV-1 Infection and Increases during Disease Progression

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Ultrastructural localisation of sialoadhesin (Siglec-1) on macrophages in rodent lymphoid tissues

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