Comparative genetics and innate immune functions of collagenous lectins in animals Brandon N. Lillie, Andrew S. Brooks, Natalie D. Keirstead, M. Anthony Hayes * Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ont., Canada N1G 2W1 Abstract Collagenous lectins such as mannan-binding lectins (MBLs), ficolins (FCNs), surfactant proteins A and D (SP-A, SP-D), conglutinin (CG), and related ruminant lectins are multimeric proteins with carbohydrate-binding domains aligned in a manner that facilitates binding to microbial surface polysaccharides. MBLs and FCNs are structurally related to C1q, but activate the lectin complement pathway via interaction with MBL-associated serine proteases (MASPs). MBLs, FCNs, and other collagenous lectins also bind to some host macromolecules and contribute to their removal. While there is evidence that some lectins and the lectin complement pathway are conserved in vertebrates, many differences in collagenous lectins have been observed among humans, rodents, and other vertebrates. For example, humans have only one MBL but three FCNs, whereas most other species express two FCNs and two MBLs. Bovidae express CG and other SP-D-related collectins that are not found in monogastric species. Some dysfunctions of human MBL are due to single nucleotide polymorphisms (SNPs) that affect its expression or structure and thereby increase susceptibility to some infections. Collagenous lectins have well-established roles in innate immunity to various microorganisms, so it is possible that some lectin genotypes or induced phenotypes influence resistance to some infectious or inflammatory diseases in animals. # 2005 Elsevier B.V. All rights reserved. Keywords: Lectins; Collectins; Ficolins; Innate immunity; Polymorphisms; Complement 1. Introduction The innate immune system of vertebrates employs a relatively small set of proteins that can interact with a wide range of microbial surface polysaccharides. These include collectins, ficolins, C1q, galectins, pentraxins, natural antibodies, and various other humoral or cell membrane-associated factors (Ochsenbein and Zinker- nagel, 2000; Kishore and Reid, 2000; East and Isacke, 2002; Dahms and Hancock, 2002; Kilpatrick, 2002; Holmskov et al., 2003; van de Wetering et al., 2004). Some of these microbial polysaccharide-binding www.elsevier.com/locate/vetimm Veterinary Immunology and Immunopathology 108 (2005) 97–110 Abbreviations: APP, Actinobacillus pleuropneumoniae; CG, conglutinin; CL-43, collectin-43; CL-46, collectin-46; CL-L1, col- lectin liver 1; CL-P1, collectin placenta 1; CRD, carbohydrate- recognition domain; FCN, ficolin; GlcNAc, N-acetyl-D-glucosa- mine; MASP, MBL-associated serine protease; MBL, mannan-bind- ing lectin; PAMP, pathogen-associated molecular pattern; PRM, pattern recognition molecule; PRR, pattern recognition receptor; SNP, single nucleotide polymorphism; SP-A, surfactant protein A; SP-D, surfactant protein D; TLR, Toll-like receptor * Corresponding author. Tel.: +1 519 824 4120x54637; fax: +1 519 824 5930. E-mail address: ahayes@uoguelph.ca (M.A. Hayes). 0165-2427/$ – see front matter # 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.vetimm.2005.07.001