The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
Regulation of Toll-like receptor–mediated inflammatory response by complement in vivo
Open accessAbstract
Toll-like receptors (TLRs) and complement are 2 components of innate immunity that are critical for first-line host defense and elicitation of adaptive immune responses. Many pathogen-associated molecular patterns activate both TLR and complement, but whether and how these 2 systems, when coactivated in vivo, interact with each other has not been well studied. We demonstrate here a widespread regulation of TLR signaling by complement in vivo. The TLR ligands lipopolysacharride (TLR4), zymosan (TLR2/6), and CpG oligonucleotide (TLR9) caused, in a complement-dependent manner, strikingly elevated plasma interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and IL-1β, and/or decreased plasma IL-12 levels in mice deficient in the membrane complement inhibitor decay-accelerating factor (DAF). A similar outcome was observed in wild-type mice cotreated with the TLR ligands and cobra venom factor, a potent complement activator. The regulatory effect of complement on TLR-induced cytokine production in vivo was mediated by the anaphylatoxin receptors C5aR and C3aR. Additionally, changes in lipopolysaccharide (LPS)–induced cytokine production in DAF-deficient mice correlated with increased mitogen-activated protein kinase and nuclear factor-κB activation in the spleen. These results reveal a strong interaction between complement and TLR signaling in vivo and suggest a novel mechanism by which complement promotes inflammation and modulates adaptive immunity.
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Cites
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Cited by
Complement: a key system for immune surveillance and homeostasis
Ricklin, D., Hajishengallis, G., Yang, K., & Lambris, J. D. (2010) · Nature Immunology · doi:10.1038/ni.1923 · Cited by 3,654
Self-citationComplement and its role in innate and adaptive immune responses
Dunkelberger, J. R., & Song, W.-C. (2010) · Cell Research · doi:10.1038/cr.2009.139 · Cited by 1,932
Self-citationComplement System Part II: Role in Immunity
Merle, N. S., Noe, R., Halbwachs-Mecarelli, L., Fremeaux-Bacchi, V., & Roumenina, L. T. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00257 · Cited by 1,051
NLRP3 Inflammasome and the IL-1 Pathway in Atherosclerosis
Grebe, A., Hoss, F., & Latz, E. (2018) · Circulation Research · doi:10.1161/circresaha.118.311362 · Cited by 926
The role of the anaphylatoxins in health and disease
Klos, A., Tenner, A. J., Johswich, K.-O., Ager, R. R., Reis, E. S., & Köhl, J. (2009) · Molecular Immunology · doi:10.1016/j.molimm.2009.04.027 · Cited by 730
Metadata
- Authors
- Zhang, X., Kimura, Y., Fang, C., Zhou, L., Sfyroera, G., Lambris, J. D., Wetsel, R. A., Miwa, T., & Song, W.-C.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2007-07-01
- Volume
- 110
- Issue
- 1
- Pages
- 228-236
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2107489987
- Cited by
- 373
- References
- 47
- FWCI
- 8.78
- Type
- journal article
- Language
- en
- Open access
- green
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