C-Type Lectin Receptors in Host Defense Against Bacterial Pathogens

Abstract

Antigen-presenting cells (APCs) are present throughout the human body-in tissues, at barrier sites and in the circulation. They are critical for processing external signals to instruct both local and systemic responses toward immune tolerance or immune defense. APCs express an extensive repertoire of pattern-recognition receptors (PRRs) to detect and transduce these signals. C-type lectin receptors (CLRs) comprise a subfamily of PRRs dedicated to sensing glycans, including those expressed by commensal and pathogenic bacteria. This review summarizes recent findings on the recognition of and responses to bacteria by membrane-expressed CLRs on different APC subsets, which are discussed according to the primary site of infection. Many CLR-bacterial interactions promote bacterial clearance, whereas other interactions are exploited by bacteria to enhance their pathogenic potential. The discrimination between protective and virulence-enhancing interactions is essential to understand which interactions to target with new prophylactic or treatment strategies. CLRs are also densely concentrated at APC dendrites that sample the environment across intact barrier sites. This suggests an-as yet-underappreciated role for CLR-mediated recognition of microbiota-produced glycans in maintaining tolerance at barrier sites. In addition to providing a concise overview of identified CLR-bacteria interactions, we discuss the main challenges and potential solutions for the identification of new CLR-bacterial interactions, including those with commensal bacteria, and for in-depth structure-function studies on CLR-bacterial glycan interactions. Finally, we highlight the necessity for more relevant tissue-specific in vitro, in vivo and ex vivo models to develop therapeutic applications in this area.

Pattern recognition receptors in health and diseases

“… 151 Transmembrane receptors can be divided into type I and type II according to their topological structure. 152 , 153 The N-terminal of type I receptors points to extracellular and contains multiple CRDs, while the N-terminal of type II receptors points to intracellular and contains only one CRD. 154 , 155 It has been shown that the vast majority of CLRs are involved in the presentation of antigens as active membrane-associated receptors, and CLRs are mainly expressed on antigen-presenting cells such as DCs and macrophages.…”

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

“…Many innate immune cells express a wide variety of CLRs, which differ between cell types, allowing specific adjustments of the immune response upon target recognition. Thus, CLRs such as Dectin-2, Mincle, MGL (Macrophage galactose lectin), Langerin and DC-SIGN (Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin) are major players in the recognition of pathogenic fungi, bacteria, parasites and viruses [3][4][5][6]. The interaction of these CLRs with their ligands allows DCs to modulate the immune response towards either activation or tolerance [7].…”

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

“…Many innate immune cells express a wide variety of CLRs, which differ between cell types, allowing specific adjustments of the immune response upon target recognition. Thus, CLRs such as Dectin-2, Mincle, MGL (Macrophage galactose lectin), Langerin and DC-SIGN are major players in the recognition of pathogenic fungi, bacteria, parasites and viruses (de Jong et al, 2010;van Kooyk and Geijtenbeek, 2003;Mnich et al, 2020;Van Breedam et al, 2014). The interaction of these CLRs with their ligands allows dendritic cells (DC) to modulate the immune response towards either activation or tolerance.…”