Immune system transcriptome in gingival tissues of young nonhuman primates

Abstract

Young/adolescent humans demonstrate many microorganisms associated with periodontal disease in adults and substantial gingival inflammatory responses. However, younger individuals do not demonstrate the soft and hard tissue destruction that hallmark periodontitis. This study evaluated responses to the oral microbial ecology in gingival tissues from clinically healthy young Macaca mulatta (<3 years old) compared to older animals (5-23 years old). Global transcriptional profiling of four age groups revealed a subset of 159 genes that were differentially expressed at least across one of the age comparisons. Correlation metrics generated a relevance network abstraction of these genes. Partitioning of the relevance network revealed seven distinct communities comprising functionally related genes associated with host inflammatory and immune responses. A group of genes were identified that were selectively increased/decreased or positively/negatively correlated with gingival profiles in the animals. A Principal Components Analysis created metagenes of expression profiles for classifying the 23 animals. The results provide novel system-level insights into gene expression differences in healthy young tissues weighted towards host responses that were associated with anti-inflammatory biomolecules or those linked with T cell regulation of responses. The combination of the regulated microenvironment may help to explain the apparent “resistance” of younger individuals to developing periodontal disease.

Complement inhibition in pre-clinical models of periodontitis and prospects for clinical application

“…Chronic periodontitis typically affects adults, and aging is associated with increased prevalence and severity of periodontitis, which might be attributed, in part, to alterations of the immuno-inflammatory status of the periodontal tissue [74]. This hypothesis is consistent with recent studies in rhesus monkeys showing age-dependent differential expression of immune and inflammatory genes in the periodontium [75, 76]. Cynomolgus monkeys with naturally-occurring periodontitis (selected by screening a population of adult animals in the Simian Conservation Breeding and Research Center; Makati, Philippines) were locally injected in the gingiva with Cp40 either once a week (5 animals) or three times per week (10 animals) for six weeks followed by a 6-week follow-up period without Cp40 treatment.…”

Hypoxia‐inducible transcription factors, HIF1A and HIF2A, increase in aging mucosal tissues

“…We have shown significant differences in apoptosis pathway gene expression profiles associated with aging, even in healthy gingival tissues . Differences were also noted in inflammasome gene pathways, including both receptors critical for signalling, and downstream effector functions, in antigen processing and presentation pathways, and differential expression of immune system genes …”

“…2,4 Differences were also noted in inflammasome gene pathways, including both receptors critical for signalling, and downstream effector functions, 5 in antigen processing and presentation pathways, 6 and differential expression of immune system genes. 7 The human subgingival ecology has been shown to accommodate over 700 species of bacteria 8 that differ both qualitatively and quantitatively in health, gingivitis and periodontitis. 9 These difference have been documented to relate to the capacity of pioneer microorganisms to bind to host surfaces through receptor-ligand interactions, 10 asaccharolytic species of bacteria that develop in inflamed sites related to a different nutritional microenvironment, 11 anaerobic species that emerge at diseased sites presumably reflecting environmental changes of low oxygen levels, probably resulting from inflammation-induced processes generating reactive oxygen intermediates, 12 and species of bacteria that produce a range of volatile sulphur compounds.…”

Microbiome Profiles of Ligature-Induced Periodontitis in Nonhuman Primates across the Life Span

“…Nevertheless, rather minimal data are available documenting the breadth and depth of the oral microbiome in these animal species, although a recent report by Ocon et al (25) clearly demonstrates the component similarity and genomic correspondence of the microbiomes between humans and macaque monkeys. As important to this investigation, the vast majority of these data have been derived from adult or aged monkeys, with little information on the oral microbiology of younger animals (59).…”