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Evolution of the lectin–complement pathway and its role in innate immunity

Nature Reviews Immunology volume 2, pages 346–353 (2002)Cite this article

Key Points

  • Lectins, which are carbohydrate-binding proteins, are important in innate immunity because they are able to recognize a wide range of pathogens. Two classes of collagenous lectin — mannose-binding lectin (MBL) and ficolins — can activate the complement system, which was identified originally as an antibody-dependent effector system.

  • The complement system, which consists of more than 30 plasma and cell-surface proteins, is activated by three pathways — the classical, lectin and alternative pathways — which lead to the generation of opsonins and pathogen destruction.

  • The classical pathway is activated by binding of the first complement component — which consists of C1q and two serine proteases (C1r and C1s) — to immune complexes, whereas the lectin pathway is activated by the recognition of carbohydrates on pathogens through MBL and ficolins, which are associated with novel serine proteases.

  • MBL-associated serine proteases (MASPs), which share domain structure and several functions with the classical-pathway proteases C1r and C1s, are the proteolytic enzymes that are responsible for activation of the lectin pathway.

  • The ascidian complement system — which consists of MBL-like lectin, ficolins, two MASPs, C3 and C3 receptor — functions in an opsonic manner, and it constitutes a primordial complement system that corresponds to the mammalian lectin pathway.

  • Structural and functional similarities between the lectin–protease complex in the lectin pathway and the first component of the classical complement pathway indicate that the primitive lectin pathway in innate immunity might have evolved into the classical pathway to serve as an effector system of acquired immunity.

Abstract

Discrimination between self and non-self by lectins (carbohydrate-binding proteins) is a strategy of innate immunity that is found in both vertebrates and invertebrates. In vertebrates, immune recognition mediated by ficolins (lectins that consist of a fibrinogen-like and a collagen-like domain), as well as by mannose-binding lectins, triggers the activation of the complement system, which results in the activation of novel serine proteases. The presence of a similar lectin-based complement system in ascidians, our closest invertebrate relatives, indicates that the complement system probably had a pivotal role in innate immunity before the evolution of an adaptive immune system in jawed vertebrates.

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Figure 1: Activation of the classical, lectin and alternative pathways.
Figure 2: Domain and oligomeric structure of mannose-binding lectin and ficolins.
Figure 3: The complement system from an evolutionary perspective.
Figure 4: Domain structure of the MASP family.
Figure 5: Gene organization of the MASP family.
Figure 6: Putative model of an ancient lectin-based complement system and its evolution.

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Acknowledgements

This work was supported by grants from the Ministry of Education, Culture, Sport, Science and Technology, and the Japanese Society for the Promotion of Science. I thank Y. Endo, M. Matsushita and M. Takahashi for helpful discussions and sharing of unpublished data.

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Authors and Affiliations

  1. Department of Biochemistry, Fukushima Medical University School of Medicine, 1 Hikarigao-ka, Fukushima, 960-1295, Japan

    Teizo Fujita

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DATABASES

InterPro

CUB domain

CRD

EGF-like domain

fibrinogen-like domain

serine-protease domain

LocusLink

C1q

C1r

C1s

C2

C3

C4

factor B

factor D

fibrinogen-β

fibrinogen-γ

ficolins

H-ficolin

L-ficolin/P35

M-ficolin

MAC

MASP1

MASP2

MBL

TGF-β1

Glossary

C-TYPE LECTIN

A calcium-dependent animal lectin that is a carbohydrate-binding protein. The binding activity of a C-type lectin is based on the structure of the carbohydrate-recognition domain, which is highly conserved among this family. Calcium is essential not only for the carbohydrate binding itself, but also for the structural maintenance of this domain.

COLLECTIN

A C-type lectin that has a collagen-like domain. One group, the secreted lectins, consists of mannose-binding lectin, bovine conglutinin and collectin 43 in blood, and the two mucosal-associated proteins surfactant proteins A and D. The other group consists of the newly discovered, non-secreted-type collectin liver-1 and membrane-type collectin placenta-1.

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Fujita, T. Evolution of the lectin–complement pathway and its role in innate immunity. Nat Rev Immunol 2, 346–353 (2002). https://doi.org/10.1038/nri800

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