Novel Mechanisms and Functions of Complement

Overview

Journal Nat Immunol

Date 2017 Nov 17

PMID 29144501

Citations 234

Authors

George Hajishengallis

Edimara S Reis

Dimitrios C Mastellos

Daniel Ricklin

John D Lambris

Affiliations

Soon will be listed here.

Abstract

Progress at the beginning of the 21st century transformed the perception of complement from that of a blood-based antimicrobial system to that of a global regulator of immunity and tissue homeostasis. More recent years have witnessed remarkable advances in structure-function insights and understanding of the mechanisms and locations of complement activation, which have added new layers of complexity to the biology of complement. This complexity is readily reflected by the multifaceted and contextual involvement of complement-driven networks in a wide range of inflammatory and neurodegenerative disorders and cancer. This Review provides an updated view of new and previously unanticipated functions of complement and how these affect immunity and disease pathogenesis.

Citing Articles

Complosome Regulates Hematopoiesis at the Mitochondria Level.

Konopko A, Lukomska A, Ratajczak J, Kucia M, Ratajczak M Stem Cell Rev Rep. 2025; .

PMID: 40053308 DOI: 10.1007/s12015-025-10856-1.

Terminal complement complexes with or without C9 potentiate antimicrobial activity against .

Lamb E, Criss A bioRxiv. 2025; .

PMID: 39868146 PMC: 11760736. DOI: 10.1101/2025.01.16.633325.

A bipartite bacterial virulence factor targets the complement system and neutrophil activation.

Kurniyati K, Clark N, Wang H, Deng Y, Sze C, Visser M EMBO J. 2025; 44(4):1154-1184.

PMID: 39753953 PMC: 11833123. DOI: 10.1038/s44318-024-00342-8.

Natural antibodies to polysaccharide capsules enable Kupffer cells to capture invading bacteria in the liver sinusoids.

Tian X, Liu Y, Zhu K, An H, Feng J, Zhang L J Exp Med. 2024; 222(2).

PMID: 39718543 PMC: 11668174. DOI: 10.1084/jem.20240735.

Prospects for potential therapy targeting immune‑associated factors in endometriosis (Review).

Zhang W, Li K, Jian A, Zhang G, Zhang X Mol Med Rep. 2024; 31(3.

PMID: 39717957 PMC: 11715623. DOI: 10.3892/mmr.2024.13422.

References

Arbore G, Kemper C, Kolev M . Intracellular complement - the complosome - in immune cell regulation. Mol Immunol. 2017; 89:2-9. PMC: 7112704. DOI: 10.1016/j.molimm.2017.05.012. View

Liu H, Fergusson M, Castilho R, Liu J, Cao L, Chen J . Augmented Wnt signaling in a mammalian model of accelerated aging. Science. 2007; 317(5839):803-6. DOI: 10.1126/science.1143578. View

Doerner S, Reis E, Leung E, Ko J, Heaney J, Berger N . High-Fat Diet-Induced Complement Activation Mediates Intestinal Inflammation and Neoplasia, Independent of Obesity. Mol Cancer Res. 2016; 14(10):953-965. PMC: 5330314. DOI: 10.1158/1541-7786.MCR-16-0153. View

Forneris F, Ricklin D, Wu J, Tzekou A, Wallace R, Lambris J . Structures of C3b in complex with factors B and D give insight into complement convertase formation. Science. 2011; 330(6012):1816-20. PMC: 3087196. DOI: 10.1126/science.1195821. View

Maekawa T, Abe T, Hajishengallis E, Hosur K, DeAngelis R, Ricklin D . Genetic and intervention studies implicating complement C3 as a major target for the treatment of periodontitis. J Immunol. 2014; 192(12):6020-7. PMC: 4078411. DOI: 10.4049/jimmunol.1400569. View

Cardone J, Le Friec G, Vantourout P, Roberts A, Fuchs A, Jackson I . Complement regulator CD46 temporally regulates cytokine production by conventional and unconventional T cells. Nat Immunol. 2010; 11(9):862-71. PMC: 4011020. DOI: 10.1038/ni.1917. View

Cho M, Rupaimoole R, Choi H, Noh K, Chen J, Hu Q . Complement Component 3 Is Regulated by TWIST1 and Mediates Epithelial-Mesenchymal Transition. J Immunol. 2016; 196(3):1412-8. PMC: 4724537. DOI: 10.4049/jimmunol.1501886. View

Wang Y, Sun S, Liu Q, Yu Y, Guo J, Wang K . Autocrine Complement Inhibits IL10-Dependent T-cell-Mediated Antitumor Immunity to Promote Tumor Progression. Cancer Discov. 2016; 6(9):1022-35. PMC: 5010476. DOI: 10.1158/2159-8290.CD-15-1412. View

Ricklin D, Lambris J . Complement in immune and inflammatory disorders: pathophysiological mechanisms. J Immunol. 2013; 190(8):3831-8. PMC: 3623009. DOI: 10.4049/jimmunol.1203487. View

10.

Nabizadeh J, Manthey H, Steyn F, Chen W, Widiapradja A, Md Akhir F . The Complement C3a Receptor Contributes to Melanoma Tumorigenesis by Inhibiting Neutrophil and CD4+ T Cell Responses. J Immunol. 2016; 196(11):4783-92. DOI: 10.4049/jimmunol.1600210. View

11.

van Lookeren Campagne M, Strauss E, Yaspan B . Age-related macular degeneration: Complement in action. Immunobiology. 2016; 221(6):733-9. DOI: 10.1016/j.imbio.2015.11.007. View

12.

Papanastasiou M, Koutsogiannaki S, Sarigiannis Y, Geisbrecht B, Ricklin D, Lambris J . Structural Implications for the Formation and Function of the Complement Effector Protein iC3b. J Immunol. 2017; 198(8):3326-3335. PMC: 5478675. DOI: 10.4049/jimmunol.1601864. View

13.

Thurman J . Complement in kidney disease: core curriculum 2015. Am J Kidney Dis. 2014; 65(1):156-68. PMC: 4272665. DOI: 10.1053/j.ajkd.2014.06.035. View

14.

Haines J, Hauser M, Schmidt S, Scott W, Olson L, Gallins P . Complement factor H variant increases the risk of age-related macular degeneration. Science. 2005; 308(5720):419-21. DOI: 10.1126/science.1110359. View

15.

Hajishengallis G, Abe T, Maekawa T, Hajishengallis E, Lambris J . Role of complement in host-microbe homeostasis of the periodontium. Semin Immunol. 2013; 25(1):65-72. PMC: 3706506. DOI: 10.1016/j.smim.2013.04.004. View

16.

Clevers H . Wnt/beta-catenin signaling in development and disease. Cell. 2006; 127(3):469-80. DOI: 10.1016/j.cell.2006.10.018. View

17.

Hageman G, Anderson D, Johnson L, Hancox L, Taiber A, Hardisty L . A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration. Proc Natl Acad Sci U S A. 2005; 102(20):7227-32. PMC: 1088171. DOI: 10.1073/pnas.0501536102. View

18.

Khameneh H, Ho A, Laudisi F, Derks H, Kandasamy M, Sivasankar B . C5a Regulates IL-1β Production and Leukocyte Recruitment in a Murine Model of Monosodium Urate Crystal-Induced Peritonitis. Front Pharmacol. 2017; 8:10. PMC: 5253373. DOI: 10.3389/fphar.2017.00010. View

19.

Balkwill F, Mantovani A . Cancer-related inflammation: common themes and therapeutic opportunities. Semin Cancer Biol. 2012; 22(1):33-40. DOI: 10.1016/j.semcancer.2011.12.005. View

20.

Vasek M, Garber C, Dorsey D, Durrant D, Bollman B, Soung A . A complement-microglial axis drives synapse loss during virus-induced memory impairment. Nature. 2016; 534(7608):538-43. PMC: 5452615. DOI: 10.1038/nature18283. View