Journal article
Innate Immune Responses in Lupus-Prone Palmerston North Mice: Differential Responses to LPS and Bacterial DNA/CpG Oligonucleotides
Journal of clinical immunology, Vol.23(3), pp.202-213
05/2003
DOI: 10.1023/A:1023361912950
PMID: 12797542
Abstract
Inadequate immune response to infectious danger may contribute to the pathogenesis of systemic autoimmune diseases, e.g., systemic lupus erythematosus. To test this hypothesis, we studied innate responses of prediseased lupus-prone Palmerston North (PN) mice to lipopolysaccharide (LPS), bacterial DNA, and synthetic CpG oligonucleotides. LPS and bacterial DNA/CpG oligodeoxyribonucleotides (ODNs) drove PN splenocytes into the cell cycle and protected B cells against spontaneous apoptosis, as in control lupus-free DBA-1 mice. LPS induced significantly higher IL-6 production in PN than in control splenocytes. In contrast, in PN splenocytes bacterial DNA and CpG ODNs induced approximately four- to sixfold lower IL-12p40 and approximately twofold lower IL-6 secretion than controls. This reduction in cytokine secretion in PN mice was not due to delayed kinetics but was related to significantly higher constitutive and CpG-inducible IL-10 secretion. Neutralizing anti-IL-10 antibodies almost completely restored PN IL-6 and IL-12p40 secretion to DBA-1 levels, whereas exogenous IL-10 inhibited in vitro IL-6 and IL-12p40 production in DBA-1 mice. Importantly, treatment with either IL-10 or anti-IL-10 antibody did not modulate CpG-induced cell cycle entry and apoptosis protection in either strain. In conclusion, lupus-prone PN mice show abnormal innate responses through their pattern-recognition TLR9 receptors, characterized by higher inducible IL-10 and lower IL-12p40 and IL-6 secretion, thus implying that response to infectious danger in PN mice is inappropriate and may be linked to lupus pathogenesis.
Details
- Title: Subtitle
- Innate Immune Responses in Lupus-Prone Palmerston North Mice: Differential Responses to LPS and Bacterial DNA/CpG Oligonucleotides
- Creators
- Petar Lenert - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine University of Iowa Iowa City Iowa 52242Adam Goeken - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine University of Iowa Iowa City Iowa 52242Barry Handwerger - University of Maryland School of Medicine Baltimore MarylandRobert Ashman - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine University of Iowa Iowa City Iowa 52242
- Resource Type
- Journal article
- Publication Details
- Journal of clinical immunology, Vol.23(3), pp.202-213
- Publisher
- Kluwer Academic Publishers-Plenum Publishers
- DOI
- 10.1023/A:1023361912950
- PMID
- 12797542
- ISSN
- 0271-9142
- eISSN
- 1573-2592
- Language
- English
- Date published
- 05/2003
- Academic Unit
- Pathology; Immunology; Internal Medicine
- Record Identifier
- 9984094487302771
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