Complement System and Toll-like Receptors / TLRs

Complement System and Toll-like Receptors/TLRs (Proteins | Antibodies | Genes | ELISA Kits)

Complement Component and Compelment Receptors

Toll-like Receptors/TLRs and Complement System

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Complement System and Toll-like Receptors/TLRs Crosstalk

The complement system and toll-like receptors (TLRs) are two components of innate immunity that are critical for first-line host defense. Many pathogen-associated molecular patterns activate both complement and toll-like receptors / TLRs, and recent studies in animal models have revealed a marked synergistic interaction between the two systems. In mice deficient in a membrane complement regulator, prototypical TLR ligands such as LPS, zymosan, and polyI:C caused increased systemic complement activation, which in turn led to a profound elevation of proinflammatory cytokine biosynthesis. This phenotype required interaction between complement and TLRs because complement activation alone by cobra venom factor without TLR engagement did not lead to appreciable cytokine production. The regulatory effect of complement on TLR signaling was mediated by the anaphylatoxins C5a and C3a through a receptor-dependent mechanism and involved increased mitogen-activated protein kinase/MAPK and nuclear factor κB/NFκB activation. The crosstalk between complement system and TLRs may also impact adaptive immunity, for example, the differentiation of T helper 17 (Th-17) cells. Given that excessive activation of either TLR or complement has been associated with inflammatory tissue injury as occurs in sepsis and autoimmune diseases, the new insight on complement and TLR crosstalk may have therapeutic implications.

Complement System and Toll-like Receptors/TLRs in Atherosclerosis

Despite recent medical advances, atherosclerosis is a global burden accounting for numerous deaths and hospital admissions. Immune-mediated inflammation is a major component of the atherosclerotic process, but earlier research focus on adaptive immunity has gradually switched towards the role of innate immunity. The complement system and toll-like receptors (TLRs), and the crosstalk between them, may be of particular interest both with respect to pathogenesis and as therapeutic targets in atherosclerosis. Animal studies indicate that inhibition of C3a and C5a reduces atherosclerosis. In humans modified LDL-cholesterol activate complement system and TLRs leading to downstream inflammation, and histopathological studies indicate that the innate immune system is present in atherosclerotic lesions. Moreover, clinical studies have demonstrated that both complement system and TLRs are upregulated in atherosclerotic diseases, although interventional trials have this far been disappointing. Based on recent research showing an intimate interplay between complement system and TLRs, Hovland et al. proposed a model in which combined inhibition of both complement system and toll-like receptors / TLRs may represent a potent anti-inflammatory therapeutic approach to reduce atherosclerosis.

Complement System and Toll-like Receptors/TLRs References

1. Song W C. (2012). Crosstalk between complement and toll-like receptors. Toxicologic pathology, 40(2), 174-182.
2. Hovland A, et al. (2015). The complement system and toll-like receptors as integrated players in the pathophysiology of atherosclerosis. Atherosclerosis, 241(2), 480-494.

Complement System
Complement System Overview
Complement System Component / Protein Regulator and Receptor
Complement Genetic Feature
Complement Activation Pathways
Complement System Role
Complement System and Direct Interactions+
- Mannose Binding Lectin/MBL
Complement System Function in Immune System+
- Complement System in Adaptive Immunity
- Complement System in Innate Immunity
Complement-Dependent Cytotoxicity/CDC+
- Complement-Dependent Cytotoxicity/CDC Crossmatch
Therapeutic Target of Complement System+
- Serine Protease Inhibitors as Therapeutic Target of Complement System
- Soluble Complement Regulators as Therapeutic Target of Complement System
- Complement Component Inhibitors as Therapeutic Target of Complement System
- Anaphylatoxin Receptor Antagonists as Therapeutic Target of Complement System
- Therapeutic Antibodies of Complement System
Complement System and Toll-like Receptors / TLRs
Complement System and Coagulation
Complement Cascade and Inhibitors
Complement Evasion of Pathogens
Complement System and Antimicrobial Peptides/AMPs
Complement System and Diseases
Complement System Deficiency Diseases
Complement System Structure
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Anti-Complement Antibody Products