Neutrophil extracellular traps (NETs), are networks of extracellular DNA play a role in inflammation and infection when released in a variety of pathological conditions from lung pathologies to cancer. During efforts to elucidate NET formation and regulatory mechanisms, lectins, sugar-binding proteins, have been found to be involved NET formation or NET effects. Collectins and Pentraxins are soluble innate immune proteins that regulate NETs through regulating the NET formation process or by regulating the inflammatory effects of NETs on host tissue. Palaniyar et al. (2004) has first shown that C-type lectin surfactant protein D (SP-D) bind effectively to DNA (1), later established that SP-D can bind simultaneously to NETs and bacteria in [Douda et al., 2011] that could enhance the clearance of bacteria from the lungs (1).

C-type lectins like Dectin-1, Dectin02, and Mincle are receptors that significantly contribute to the antifungal capabilities of neutrophils and regulate the NET formation process. Sialic acid binding lectins like Siglec-9 suppress NET formation upon neutrophil binding to host sialic acids and other host molecules. From the wide variety of ways lectin can influence NETs, clear understanding of lectins in the context of NETs can provide many therapeutic strategies for a variety of pathologies. Certain lectins such as SP-D and Pentraxin 3 have been greatly elucidated such that they are being studied for treating Cystic Fibrosis and as sepsis respectively among many other pathologies. 

But there is a dearth of information regarding their pathway mechanism and feasibility of therapeutic strategies that is essential for creating therapeutic applications for diseases involving infection, inflammation, autoimmunity and more. Here we highlight what is known about lectin-NET interactions [e.g., SP-D binding to bacterial lipopolysaccharides and reducing excess NET formation in the airways; Arroyo et al., 2019], highlights some research gaps in the field, and suggests questions that can lead to greater flexibility in regulating NETs and NET-mediated diseases. 

References

1. Palaniyar N, Nadesalingam J, Clark H, Shih MJ, Dodds AW, Reid KB. Nucleic acid is a novel ligand for innate, immune pattern recognition collectins surfactant proteins A and D and mannose-binding lectin. J Biol Chem. 2004 Jul 30;279(31):32728-36. doi: 10.1074/jbc.M403763200
2. Douda DN, Jackson R, Grasemann H, Palaniyar N. Innate immune collectin surfactant protein D simultaneously binds both neutrophil extracellular traps and carbohydrate ligands and promotes bacterial trapping. J Immunol. 2011 Aug 15;187(4):1856-65. doi: 10.4049/jimmunol.1004201.
3. Arroyo R, Khan MA, Echaide M, Pérez-Gil J, Palaniyar N. SP-D attenuates LPS-induced formation of human neutrophil extracellular traps (NETs), protecting pulmonary surfactant inactivation by NETs. Commun Biol. 2019 Dec 16;2:470. doi: 10.1038/s42003-019-0662-5. eCollection 2019.