Collectins: Innate Immune Pattern Recognition Molecules

Abstract

Collectins are collagen-containing C-type (calcium-dependent) lectins which are important pathogen pattern recognising innate immune molecules. Their primary structure is characterised by an N-terminal, triple-helical collagenous region made up of Gly-X-Y repeats, an a-helical coiled-coil trimerising neck region, and a Cterminal C-type lectin or carbohydrate recognition domain (CRD). Further oligomerisation of this primary structure can give rise to more complex and multimeric structures that can be seen under electron microscope. Collectins can be found in serum as well as in a range of tissues at the mucosal surfaces. Mannanbinding lectin can activate the complement system while other members of the collectin family are extremely versatile in recognising a diverse range of pathogens via their CRDs and bring about effector functions designed at the clearance of invading pathogens. These mechanisms include opsonisation, enhancement of phagocytosis, triggering superoxidative burst and nitric oxide production. Collectins can also potentiate the adaptive immune response via antigen presenting cells such as macrophages and dendritic cells through modulation of cytokines and chemokines, thus they can act as a link between innate and adaptive immunity. This chapter describes the structure-function relationships of collectins, their diverse functions, and their interaction with viruses, bacteria, fungi and parasites.

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“…The enrichment of KEGG signaling pathways showed that the relevant action pathways related to the immune system mainly included Toll-like receptor (TLR) signaling, T cell receptor signaling, B cell receptor signaling, and Jak-STAT signaling pathways. Recent studies have shown that innate immunity is an important body immunity, and the pattern recognition receptor fam-ily (PRR) is necessary for the natural immune re-sponse to recognize microbial pathogens; the multiple conservative points of pathogen recognition are called pathogen-related molecular patterns (PAMP) [ 22 ] . TLRs, the first members of the PRR fam-ily widely present in the immune system, can spe-cifically identify pathogenic microorganisms and transmit extracellular antigen recognition informa-tion into cells [ 23 ] .…”

Therapeutic Targeting of the Complement System: From Rare Diseases to Pandemics

“…In addition, the lung surfactant protein (SP)-A and SP-D also belong to the collectin family. However, they do not activate the complement system ( Tenner et al, 1989 ), as reviewed in Murugaiah et al (2020) . The protein CL-12 (also called collectin placenta 1 or CL-P1) may be included in the family ( Hansen et al, 2016 ).…”

Bovine Collectins: Role in Health and Disease

“…The N-terminal regions have 1–3 cysteine residues that can form disulphide links, cross-linking the collagen regions, which are comprised of three polypeptide chains and can be further organised into large oligomeric structures composed of a maximum of six subunits (Hansen and Holmskov 2002 ). Collectins are soluble pattern recognition receptors (PPRs) specialised at recognising pathogen-associated molecular pattern (PAMPs) of carbohydrate moieties such as lipopolysaccharide (LPS) that are present on microbial surfaces (Janeway 1989 ; Hansen and Holmskov 1998 ; Murugaiah et al 2020 ). Recognition and binding occur via the CRD regions and can lead to pathogen agglutination, neutralization and/or clearance by opsonization of the microbe and recruitment of phagocytes for clearance (Kishore et al 2006 ; Murugaiah et al 2020 ).…”

“…Collectins are soluble pattern recognition receptors (PPRs) specialised at recognising pathogen-associated molecular pattern (PAMPs) of carbohydrate moieties such as lipopolysaccharide (LPS) that are present on microbial surfaces (Janeway 1989 ; Hansen and Holmskov 1998 ; Murugaiah et al 2020 ). Recognition and binding occur via the CRD regions and can lead to pathogen agglutination, neutralization and/or clearance by opsonization of the microbe and recruitment of phagocytes for clearance (Kishore et al 2006 ; Murugaiah et al 2020 ). Mice engineered to be genetically deficient in SP-A or SP-D showed increased susceptibility to microbial infections (Levine and Whitsett 2001 ).…”

“…The study of bovine collectins and their specific role in bovine infectious disease has been neglected. In comparison, collectin immunobiology is well understood in human and other model systems (e.g., mice) (Murugaiah et al 2020 ). In this review, the current knowledge on bovine collectins will be summarised but also gaps in current knowledge will be discussed with respect to findings in human and other mammalian species.…”