Siglecs at the Host–Pathogen Interface

Chang, Yung-Chi; Nizet, Victor

doi:10.1007/978-981-15-1580-4_8

Cited by 30 publications

(28 citation statements)

References 104 publications

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“…A detailed discussion of lectins outside the plant world, is beyond the scope of this review. For more information on lectins from viruses, bacteria, fungi, algae, invertebrates and vertebrates, their molecular structures and biological importance we refer to several recent review papers [162][163][164][165][166][167][168][169][170][171].…”

Section: Similarities and Differences Between Plant Lectins And Lectimentioning

confidence: 99%

130 years of Plant Lectin Research

2020

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Lectins are proteins with diverse molecular structures that share the ability to recognize and bind specifically and reversibly to carbohydrate structures without changing the carbohydrate moiety. The history of lectins started with the discovery of ricin about 130 years ago but since then our understanding of lectins has dramatically changed. Over the years the research focus was shifted from 'the characterization of carbohydrate-binding proteins' to 'understanding the biological function of lectins'. Nowadays plant lectins attract a lot of attention especially because of their potential for crop improvement and biomedical research, as well as their application as tools in glycobiology. The present review aims to give an overview of plant lectins and their applications, and how the field evolved in the last decades.

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Section: Similarities and Differences Between Plant Lectins And Lectimentioning

confidence: 99%

130 years of Plant Lectin Research

2020

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“…The demography of severe disease is compatible with a known viral mechanism, binding of sialylated secreted glycans to host sialic acid-binding immunoglobulin-type lectins (Siglecs) [3] . This interaction can allow immune evasion and immunosuppression [4] .…”

Section: Potential Binding Of Sars-cov-2 Secreted Glycans To Cd33-relmentioning

confidence: 95%

“…Both CD33 and Siglec-5 are significantly bound by sialyl-Tn [6] , [9] . Sialyl Tn glycan binding is a functionally important modulator of CD33 signalling, as identified for HIV envelope glycoprotein Gp120 [3] .…”

Section: Known Ligands Of Cd33-related Siglecsmentioning

confidence: 99%

Common determinants of severe Covid-19 infection are explicable by SARS-CoV-2 secreted glycoprotein interaction with the CD33-related Siglecs, Siglec-3 and Siglec-5/14

Murch

2020

Medical Hypotheses

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SARS-CoV-2 interaction with the ACE-2 receptor cannot alone explain the demography and remarkable variation in clinical progression of Covid-19 infection. Unlike SARS-CoV, the cause of SARS, several SARS-CoV-2 spike glycans contain sialic acid residues. In contrast to the SARS secreted glycoprotein (SGP), SARS-CoV-2 SGP are thus potential ligands for Sialic acid-binding Siglecs on host immune cells, known to regulate immune function. Such SARS-CoV-2 glycoproteins would contribute to immune deviation. CD33-related Siglecs are important immune regulators. Siglec-5 and −14 are paired receptors with opposed actions on the NLRP3 inflammasome, which is critical in early viral clearance. SGP binding in persons of Siglec-14 null genotype (30–70% in Black, Asian and Minority Ethnic (BAME) persons, 10% in North Europeans) would induce unopposed inhibitory signalling, causing viral persistence through inflammasome inhibition. Siglec-3 (CD33) and Siglec-5 are expressed on CD33 myeloid derived suppressor cells (CD33 MDSC). Immunosuppressive CD33 MDSC populations are increased in all groups at risk of severe Covid-19 infection. CD33 expression is increased in persons with the CD33 rs3865444 CC allele, associated with Alzheimer’s disease, who would thus show enhanced susceptibility. Viral SGP ligation of CD33, potentially in conjunction with Siglec-5, would promote expansion of CD33 MDSC cells, as occurs in cancers but at much greater scale. CD33 is expressed on CNS microglia, potentially activated by SGP penetration through the porous cribriform plate to cause anosmia. Genotyping of severe or fatal Covid-19 cases can confirm or refute this pathophysiological mechanism. Early data have confirmed extremely high-level increase of CD33 MDSC numbers in severe Covid-19 infection, consistent with the proposed mechanism.

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“…Diversification of CD33-related Siglecs is probably due to interactions with pathogens exploiting inhibitory Siglec receptors by covering themselves with sialoglycans. 130 Some pathogens as the group B streptococci have even developed proteins to engage inhibitory Siglecs on myeloid cells and thereby evade immune-mediated killing. 131 …”

Section: Targeting Glycan-receptor Interactions To Improve Cancer Immmentioning

confidence: 99%

Tumor-associated carbohydrates and immunomodulatory lectins as targets for cancer immunotherapy

Mantuano

Natoli

Zippelius

et al. 2020

J Immunother Cancer

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During oncogenesis, tumor cells present specific carbohydrate chains that are new targets for cancer immunotherapy. Whereas these tumor-associated carbohydrates (TACA) can be targeted with antibodies and vaccination approaches, TACA including sialic acid-containing glycans are able to inhibit anticancer immune responses by engagement of immune receptors on leukocytes. A family of immune-modulating receptors are sialic acid-binding Siglec receptors that have been recently described to inhibit antitumor activity mediated by myeloid cells, natural killer cells and T cells. Other TACA-binding receptors including selectins have been linked to cancer progression. Recent studies have shown that glycan-lectin interactions can be targeted to improve cancer immunotherapy. For example, interactions between the immune checkpoint T cell immunoglobulin and mucin-domain containing-3 and the lectin galectin-9 are targeted in clinical trials. In addition, an antibody against the lectin Siglec-15 is being tested in an early clinical trial. In this review, we summarize the previous and current efforts to target TACA and to inhibit inhibitory immune receptors binding to TACA including the Siglec-sialoglycan axis.

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Siglecs at the Host–Pathogen Interface

Cited by 30 publications

References 104 publications

130 years of Plant Lectin Research

130 years of Plant Lectin Research

Common determinants of severe Covid-19 infection are explicable by SARS-CoV-2 secreted glycoprotein interaction with the CD33-related Siglecs, Siglec-3 and Siglec-5/14

Tumor-associated carbohydrates and immunomodulatory lectins as targets for cancer immunotherapy

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