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Characteristic changes in microbial community composition and expression of innate immune genes in acute appendicitis
Alexander Arlt1, Richa Bharti2, Imre Ilves3
1Department of Internal Medicine I, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany aarlt@1med.uni-kiel.de.
Abstract:
Appendicitis represents a common and severe gastrointestinal illness in younger individuals worldwide. The disease is characterized by an excessive inflammatory response and it is believed that bacterial overgrowth due to blockage of the appendix lumen might be involved. Despite the high incidence, only limited data on the pathophysiological changes exist; in particular, the innate immune responses involved are largely unknown. Real-time PCR analysis of tissue samples from inflamed and normal appendices demonstrated differentially regulated expression patterns of epithelial-derived antimicrobial peptides (AMP). The α-defensins human neutrophil peptides 1-3, HD5 and HD6, as well as the two β-defensins, human β-defensins (hBD)-2 and hBD-3, were up-regulated, whereas hBD-1 was down-regulated in acute appendicitis. Expression of upstream regulators of AMP expression, NOD-2 and TLRs 1, 2, 4, 5, 7, 8 and 10 was significantly increased as detected by real-time PCR. Finally, we confirmed the involvement of the pro-inflammatory cytokines IL-1β and IL-8, and detected characteristic changes in microbial community composition in appendicitis tissue specimens by 16S rDNA based detection techniques. In this study, we demonstrate a differential regulation of the innate immune system along with an altered bacterial diversity in acute appendicitis.
Insights
Acute appendicitis involves altered bacterial diversity and immune system dysregulation. Key antimicrobial peptides and immune response regulators show significant changes in inflamed appendix tissues.
Area of Science:
- Gastroenterology
- Immunology
- Microbiology
Background:
- Appendicitis is a common gastrointestinal illness with limited understanding of its underlying pathophysiology.
- The role of innate immune responses and microbial changes in acute appendicitis remains largely unknown.
Purpose of the Study:
- To investigate the differential regulation of innate immune responses in acute appendicitis.
- To analyze changes in bacterial community composition within inflamed appendix tissues.
Main Methods:
- Real-time PCR analysis of inflamed and normal appendix tissue samples.
- Detection of antimicrobial peptides (AMPs), NOD-2, TLRs, IL-1β, and IL-8 expression.
- 16S rDNA-based techniques to assess microbial community composition.
Main Results:
- Differential expression of epithelial-derived antimicrobial peptides (AMPs), including up-regulation of α-defensins (HD5, HD6) and β-defensins (hBD-2, hBD-3), and down-regulation of hBD-1.
- Significant increase in the expression of upstream regulators of AMPs, such as NOD-2 and Toll-like receptors (TLRs 1, 2, 4, 5, 7, 8, 10).
- Confirmation of pro-inflammatory cytokine involvement (IL-1β, IL-8) and altered bacterial diversity in appendicitis specimens.
Conclusions:
- Acute appendicitis is characterized by significant dysregulation of the innate immune system.
- Altered bacterial diversity is a key feature of acute appendicitis, alongside specific changes in immune mediator expression.
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