The versatile functions of complement C3‐derived ligands

Erdei, Anna; Sándor, Noémi; Mácsik-Valent, Bernadett; Lukácsi, Szilvia; Kremlitzka, Mariann; Bajtay, Zsuzsa

doi:10.1111/imr.12498

Cited by 31 publications

(23 citation statements)

References 157 publications

(267 reference statements)

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“…Independent of the route of initiation, opsonization with C3b marks the starting point for the generation of a series of potent effectors with the aim of facilitating the clearance of the tagged particles (Figure D). In this context, C3b not only amplifies the complement response via convertase formation but also acts as an effector itself that mediated functions in innate and adaptive immunity . Via binding to complement receptor 1 (CR1; CD35) on immune cells, it confers immune adherence that enables the shuttling of opsonized cells to the spleen and liver.…”

Section: Complement C3: a Functional Hub In Innate Immunity And Beyondmentioning

confidence: 99%

“…In this context, C3b not only amplifies the complement response via convertase formation but also acts as an effector itself that mediated functions in innate and adaptive immunity. 12 Via binding to complement receptor 1 (CR1; CD35) on immune cells, it confers immune adherence that enables the shuttling of opsonized cells to the spleen and liver. Tissue-resident macrophages such as Kupffer cells in the liver also express the complement receptor of the immunoglobulin family (CRIg) that has been shown to bind C3b and induce phagocytosis.…”

Section: Independent Of the Route Of Initiation Opsonization With C3bmentioning

confidence: 99%

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Complement component C3 – The “Swiss Army Knife” of innate immunity and host defense

Ricklin

Reis

Mastellos

et al. 2016

Immunological Reviews

322

295

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Summary As a preformed defense system, complement faces a delicate challenge in providing an immediate, forceful response to pathogens even at first encounter, while sparing host cells in the process. For this purpose, it engages a tightly regulated network of plasma proteins, cell surface receptors, and regulators. Complement component C3 plays a particularly versatile role in this process by keeping the cascade alert, acting as a point of convergence of activation pathways, fueling the amplification of the complement response, exerting direct effector functions, and helping to coordinate downstream immune responses. In recent years, it has become evident that nature engages the power of C3 not only to clear pathogens but also for a variety of homeostatic processes ranging from tissue regeneration and synapse pruning to clearing debris and controlling tumor cell progression. At the same time, its central position in immune surveillance makes C3 a target for microbial immune evasion and, if improperly engaged, a trigger point for various clinical conditions. In our review, we look at the versatile roles and evolutionary journey of C3, discuss new insights into the molecular basis for C3 function, provide examples of disease involvement, and summarize the emerging potential of C3 as a therapeutic target.

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Section: Complement C3: a Functional Hub In Innate Immunity And Beyondmentioning

confidence: 99%

Section: Independent Of the Route Of Initiation Opsonization With C3bmentioning

confidence: 99%

Complement component C3 – The “Swiss Army Knife” of innate immunity and host defense

Ricklin

Reis

Mastellos

et al. 2016

Immunological Reviews

322

295

View full text Add to dashboard Cite

show abstract

“…C3b behaves as an opsonin that gets deposited onto target surfaces though formation of an amide or ester bond between its exposed active thioester and available amino-acid or carbohydrate moieties. Once opsonized, C3b and its potential byproducts can be recognized by adequate receptors present on the surface of various phagocytic cells [34]. Unlike C3b, C3a is an anaphylatoxin.…”

Section: The Complement Systemmentioning

confidence: 99%

Regulation of anti-microbial autophagy by factors of the complement system

Viret¹,

Rozières²,

Duclaux-Loras³

et al. 2020

Microb Cell

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The complement system is a major component of innate immunity that participates in the defense of the host against a myriad of pathogenic microorganisms. Activation of complement allows for both local inflammatory response and physical elimination of microbes through phagocytosis or lysis. The system is highly efficient and is therefore finely regulated. In addition to these well-established properties, recent works have revealed that components of the complement system can be involved in a variety of other functions including in autophagy, the conserved mechanism that allows for the targeting and degradation of cytosolic materials by the lysosomal pathway after confining them into specialized organelles called autophagosomes. Besides impacting cell death, development or metabolism, the complement factors-autophagy connection can greatly modulate the cell autonomous, antimicrobial activity of autophagy: xenophagy. Both surface receptorligand interactions and intracellular interactions are involved in the modulation of the autophagic response to intracellular microbes by complement factors. Here, we review works that relate to the recently discovered connections between factors of the complement system and the functioning of autophagy in the context of host-pathogen relationship. Abbreviations:ATG -autophagy-related factor; CD4 T -mature T lymphocytes of the CD4 lineage; C3aR -C3a receptor; C5aR -C5a receptor; EGF-epidermal growth factor; GAS -group A Streptococcus; GOPC -Golgi-associated PDZ and Coiled-Coil Motif containing; GTPases -guanosine triphosphate hydrolase; LC3 (MAP1LC3) -microtubuleassociated protein 1-light chain 3; Mcrmacroglobulin complement-related; mTORC1mammalian target of rapamycin complex 1; MACmembrane attack complex (C5b-9); MASP -MBLassociated serine proteases; MAVS -mitochondrial antiviral signaling; MBL -mannan-binding lectin; MCP -membrane cofactor protein (CD46); MEGF10 -multiple epidermal growth factor-like domain factor 10; MeV -Measles virus; NF-κB -nuclear factor-kappa B; PI(3)P -phosphatidylinositol 3phosphate; RCA -regulators of complement activation; ULK1 -Unc51-like kinase; VPSvacuolar protein sorting.C. Viret et al. (2020) Complement-mediated regulation of xenophagy OPEN ACCESS | www.microbialcell.com 94

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“…The complement system is a major part of the immune system, present in various organs such as the heart, lung, liver, kidney and gut [1,2]. This system activates alternative regulation of the complement cascade of three different pathways including the classical, lectin and alternative pathways, subsequently resulting in elimination of the antigenic agent [2].…”

Section: Introductionmentioning

confidence: 99%

Compensatory role of C3 convertase on the strain difference for C3 protein expression in FVB/N, C3H/HeN and C57BL/6N mice

et al. 2020

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To investigate the role of complement C3 (C3) convertase on the strain difference for C3 protein expression in three inbred mice strains, we compared the levels of C2, C3 and C4 mRNA, as well as C3 protein and C3 convertase activity in the serum and liver tissue of FVB/N, C3H/HeN and C57BL/6N mice. The level of mRNA, inactive form (InACF) and active form (ACF) for C3 showed a regular pattern, which they were higher in the FVB/N and C57BL/6N mice than C3H/HeN mice. However, the level of C3b fragments (C3bα and β) derived from C3 protein were constantly maintained in the liver of FVB/N, C3H/HeN and C57BL/6N mice in spite of the strain difference on the transcriptional and translation level of C3. Especially, a reverse pattern of the level of mRNA, InACF and ACF for C3 was observed on the activity level of C3 convertase activity. The highest level of C3 convertase activity was measured in C3H/HeN mice, followed by C57BL/6N and FVB/N mice. In case of C3 convertase components, the level of C2 mRNA was higher in C3H/HeN mice than FVB/N and C57BL/6 N mice, while levels of C4 mRNA were higher in FVB/N and C57BL/6N mice than C3H/HeN mice. The current study results provide the first scientific evidence that C3 convertase may play complementary role to overcome the strain difference on the C3 protein expression in FVB/N, C3H/HeN and C57BL/6N mice.

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The versatile functions of complement C3‐derived ligands

Cited by 31 publications

References 157 publications

Complement component C3 – The “Swiss Army Knife” of innate immunity and host defense

Complement component C3 – The “Swiss Army Knife” of innate immunity and host defense

Regulation of anti-microbial autophagy by factors of the complement system

Compensatory role of C3 convertase on the strain difference for C3 protein expression in FVB/N, C3H/HeN and C57BL/6N mice

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