Navigation auf zora.uzh.ch

Search ZORA

ZORA (Zurich Open Repository and Archive)

Lymphoid follicle destruction and immunosuppression after repeated CpG oligodeoxynucleotide administration.

Heikenwalder, M; Polymenidou, M; Junt, T; Sigurdson, C; Wagner, H; Akira, S; Zinkernagel, R; Aguzzi, A (2004). Lymphoid follicle destruction and immunosuppression after repeated CpG oligodeoxynucleotide administration. Nature Medicine, 10(2):187-192.

Abstract

DNA containing unmethylated cytidyl guanosyl (CpG) sequences, which are underrepresented in mammalian genomes but prevalent in prokaryotes, is endocytosed by cells of the innate immune system, including macrophages, monocytes and dendritic cells, and activates a pathway involving Toll-like receptor-9 (TLR9). CpG-containing oligodeoxynucleotides (CpG-ODN) are potent stimulators of innate immunity, and are currently being tested as adjuvants of antimicrobial, antiallergic, anticancer and antiprion immunotherapy. Little is known, however, about the consequences of repeated CpG-ODN administration, which is advocated for some of these applications. Here we report that daily injection of 60 microg CpG-ODN dramatically alters the morphology and functionality of mouse lymphoid organs. By day 7, lymphoid follicles were poorly defined; follicular dendritic cells (FDC) and germinal center B lymphocytes were suppressed. Accordingly, CpG-ODN treatment for > or =7 d strongly reduced primary humoral immune responses and immunoglobulin class switching. By day 20, mice developed multifocal liver necrosis and hemorrhagic ascites. All untoward effects were strictly dependent on CpG and TLR9, as neither the CpG-ODN treatment of Tlr9(-/-) mice nor the repetitive challenge of wild-type mice with nonstimulatory ODN (AT-ODN) or with the TLR3 agonist polyinosinic:cytidylic acid (polyI:C) were immunotoxic or hepatotoxic.

Additional indexing

Item Type:Journal Article, refereed
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Life Sciences > General Biochemistry, Genetics and Molecular Biology
Language:English
Date:1 February 2004
Deposited On:11 Feb 2008 12:26
Last Modified:01 Nov 2024 02:37
Publisher:Nature Publishing Group
ISSN:1078-8956
OA Status:Closed
Publisher DOI:https://doi.org/10.1038/nm987
PubMed ID:14745443
Full text not available from this repository.

Metadata Export

Statistics

Citations

Dimensions.ai Metrics
385 citations in Web of Science®
415 citations in Scopus®
Google Scholar™

Altmetrics

Authors, Affiliations, Collaborations

Similar Publications