Proteins of the lectin pathway of the complement system activation: immunobiological functions, genetics and involvement in the pathogenesis of human diseases

The complement system is the most ancient components in the innate immunity, mainly functioning to primarily eliminate bacterial agents intravascularly. Moreover, the complement complex proteins play a role as a bridge between the systems of innate and adaptive immunity providing adequate conditions...

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Main Authors: Marina V. Smolnikova, Sergey Yu. Tereshchenko
Format: Article
Language:Russian
Published: Sankt-Peterburg : NIIÈM imeni Pastera 2022-05-01
Series:Инфекция и иммунитет
Subjects:
Online Access:https://iimmun.ru/iimm/article/viewFile/1777/1398
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author Marina V. Smolnikova
Sergey Yu. Tereshchenko
author_facet Marina V. Smolnikova
Sergey Yu. Tereshchenko
author_sort Marina V. Smolnikova
collection DOAJ
description The complement system is the most ancient components in the innate immunity, mainly functioning to primarily eliminate bacterial agents intravascularly. Moreover, the complement complex proteins play a role as a bridge between the systems of innate and adaptive immunity providing adequate conditions for maturation and differentiation of B- and T-lymphocytes. The complement system consists of plasma proteins and membrane receptors. Plasma proteins interact with each other via the three described cascade pathways lectin (which is most ancient phylogenetically), alternative and classical. Lectins are proteins comprising a separate superfamily of pattern-recognizing receptors able to sense molecules of oligo- and polysaccharide nature and induce their aggregation. Among all the lectins, ficolins (FCN) (common domain fibrinogen) and collectins (common domain collagen) mannose-binding lectin (MBL), hepatic and renal collectins have exert unique functions by complexing with carbohydrate components of microbial wall. Formation of a compound complex microbial wall polysaccharides + collectin/ficolin + specific mannose-binding lectin-associated serine proteases (MARP) results in the complement system activation, inflammatory reaction and bacterium elimination. Such scenario is proceeded along the lectin pathway compared to the two other pathways called classical and alternative. Examining a role of the complement system and congenital protein defects in the pathogenesis of various diseases is of topical interest because inborn deficiency of the complement components comprises at least 5% out of total primary immunodeficiency rate, whereas the aspects of their prevalence and pathogenesis remain unexplored. Relevance of investigating the complement system components for diverse populations is tremendous, taking into consideration accumulated evidence regarding an important role of the lectin pathway in viral infections. Lectins, the main proteins in the lectin pathway of the complement activation, are encoded by polymorphic genes, wherein single nucleotide polymorphisms (SNPs) result in altered protein conformation and expression, which, in turn, affects functionality and potential to respond to a pathogen. The distribution of the lectin polymorphic gene frequencies and their haplotypes displays extremely marked population differences. According to analyzing available data, population SNP frequencies including those associated with inborn deficiencies for components of the lectin pathway have been currently scarce or unexplored. hence, here we review major lectins and their functions, their functionally significant SNPs in diverse populations and their pathogenetic importance for host defense functions.
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spelling doaj.art-6cecd50e450b4b38a8480cf67c61c86a2022-12-22T03:46:13ZrusSankt-Peterburg : NIIÈM imeni PasteraИнфекция и иммунитет2220-76192313-73982022-05-0112220922110.15789/2220-7619-POT-17771130Proteins of the lectin pathway of the complement system activation: immunobiological functions, genetics and involvement in the pathogenesis of human diseasesMarina V. Smolnikova0https://orcid.org/0000-0001-9984-2029Sergey Yu. Tereshchenko1https://orcid.org/0000-0002-1605-7859Research Institute of Medical Problems of the North, Krasnoyarsk Scientific Center, Siberian Branch, Russian Academy of SciencesResearch Institute of Medical Problems of the North, Krasnoyarsk Scientific Center, Siberian Branch, Russian Academy of SciencesThe complement system is the most ancient components in the innate immunity, mainly functioning to primarily eliminate bacterial agents intravascularly. Moreover, the complement complex proteins play a role as a bridge between the systems of innate and adaptive immunity providing adequate conditions for maturation and differentiation of B- and T-lymphocytes. The complement system consists of plasma proteins and membrane receptors. Plasma proteins interact with each other via the three described cascade pathways lectin (which is most ancient phylogenetically), alternative and classical. Lectins are proteins comprising a separate superfamily of pattern-recognizing receptors able to sense molecules of oligo- and polysaccharide nature and induce their aggregation. Among all the lectins, ficolins (FCN) (common domain fibrinogen) and collectins (common domain collagen) mannose-binding lectin (MBL), hepatic and renal collectins have exert unique functions by complexing with carbohydrate components of microbial wall. Formation of a compound complex microbial wall polysaccharides + collectin/ficolin + specific mannose-binding lectin-associated serine proteases (MARP) results in the complement system activation, inflammatory reaction and bacterium elimination. Such scenario is proceeded along the lectin pathway compared to the two other pathways called classical and alternative. Examining a role of the complement system and congenital protein defects in the pathogenesis of various diseases is of topical interest because inborn deficiency of the complement components comprises at least 5% out of total primary immunodeficiency rate, whereas the aspects of their prevalence and pathogenesis remain unexplored. Relevance of investigating the complement system components for diverse populations is tremendous, taking into consideration accumulated evidence regarding an important role of the lectin pathway in viral infections. Lectins, the main proteins in the lectin pathway of the complement activation, are encoded by polymorphic genes, wherein single nucleotide polymorphisms (SNPs) result in altered protein conformation and expression, which, in turn, affects functionality and potential to respond to a pathogen. The distribution of the lectin polymorphic gene frequencies and their haplotypes displays extremely marked population differences. According to analyzing available data, population SNP frequencies including those associated with inborn deficiencies for components of the lectin pathway have been currently scarce or unexplored. hence, here we review major lectins and their functions, their functionally significant SNPs in diverse populations and their pathogenetic importance for host defense functions.https://iimmun.ru/iimm/article/viewFile/1777/1398complementlectinsmblfcnmasppolymorphismethnic differences
spellingShingle Marina V. Smolnikova
Sergey Yu. Tereshchenko
Proteins of the lectin pathway of the complement system activation: immunobiological functions, genetics and involvement in the pathogenesis of human diseases
Инфекция и иммунитет
complement
lectins
mbl
fcn
masp
polymorphism
ethnic differences
title Proteins of the lectin pathway of the complement system activation: immunobiological functions, genetics and involvement in the pathogenesis of human diseases
title_full Proteins of the lectin pathway of the complement system activation: immunobiological functions, genetics and involvement in the pathogenesis of human diseases
title_fullStr Proteins of the lectin pathway of the complement system activation: immunobiological functions, genetics and involvement in the pathogenesis of human diseases
title_full_unstemmed Proteins of the lectin pathway of the complement system activation: immunobiological functions, genetics and involvement in the pathogenesis of human diseases
title_short Proteins of the lectin pathway of the complement system activation: immunobiological functions, genetics and involvement in the pathogenesis of human diseases
title_sort proteins of the lectin pathway of the complement system activation immunobiological functions genetics and involvement in the pathogenesis of human diseases
topic complement
lectins
mbl
fcn
masp
polymorphism
ethnic differences
url https://iimmun.ru/iimm/article/viewFile/1777/1398
work_keys_str_mv AT marinavsmolnikova proteinsofthelectinpathwayofthecomplementsystemactivationimmunobiologicalfunctionsgeneticsandinvolvementinthepathogenesisofhumandiseases
AT sergeyyutereshchenko proteinsofthelectinpathwayofthecomplementsystemactivationimmunobiologicalfunctionsgeneticsandinvolvementinthepathogenesisofhumandiseases