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Title: Antibody neutralization of microbiota-derived circulating peptidoglycan dampens inflammation and ameliorates autoimmunity
Authors: Huang, Zhenxing
Wang, Jianhe
Xu, Xiaoli
Wang, Haishan
Qiao, Yuan
Chu, Wern Cui
Xu, Shengli
Chai, Louis
Cottier, Fabien
Pavelka, Norman
Oosting, Marije
Joosten, Leo A. B.
Netea, Mihai
Ng, Carol Yee Leng
Leong, Khai Pang
Kundu, Parag
Lam, Kong-Peng
Pettersson, Sven
Wang, Yue
Keywords: Science::Medicine
Issue Date: 2019
Source: Huang, Z., Wang, J., Xu, X., Wang, H., Qiao, Y., Chu, W. C., Xu, S., Chai, L., Cottier, F., Pavelka, N., Oosting, M., Joosten, L. A. B., Netea, M., Ng, C. Y. L., Leong, K. P., Kundu, P., Lam, K., Pettersson, S. & Wang, Y. (2019). Antibody neutralization of microbiota-derived circulating peptidoglycan dampens inflammation and ameliorates autoimmunity. Nature Microbiology, 4(5), 766-773.
Project: BMRC/ BnB/0001b/2012
Journal: Nature Microbiology
Abstract: The human microbiota provides tonic signals that calibrate the host immune response1,2, but their identity is unknown. Bacterial peptidoglycan (PGN) subunits are likely candidates since they are well-known immunity-enhancing adjuvants, released by most bacteria during growth, and have been found in the blood of healthy people3-7. We developed a monoclonal antibody (mAb), 2E7, that targets muramyl-L-alanyl-D-isoglutamine (MDP), a conserved and minimal immunostimulatory structure of PGN. Using 2E7-based assays, we detected PGN ubiquitously in human blood at a broad range of concentrations that is relatively stable in each individual. We also detected PGN in the serum of several warm-blooded animals. However, PGN is barely detectable in the serum of germ-free mice, indicating that its origin is the host microbiota. Neutralization of circulating PGN via intraperitoneal administration of 2E7 suppressed the development of autoimmune arthritis and experimental autoimmune encephalomyelitis in mice. Arthritic NOD2-/- mice lacking the MDP sensor did not respond to 2E7, indicating that 2E7 dampens inflammation by blocking nucleotide-binding oligomerization domain-containing protein 2 (NOD2)-mediated pathways. We propose that circulating PGN acts as a natural immune potentiator that tunes the host immune response; altering its level is a promising therapeutic strategy for immune-mediated diseases.
ISSN: 2058-5276
DOI: 10.1038/s41564-019-0381-1
Rights: © 2019 The Author(s), under exclusive licence to Springer Nature Limited. All rights reserved.
Fulltext Permission: none
Fulltext Availability: No Fulltext
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