Transcriptome Analysis of B Cell Immune Functions in Periodontitis: Mucosal Tissue Responses to the Oral Microbiome in Aging

Abstract

Evidence has shown activation of T and B cells in gingival tissues in experimental models and in humans diagnosed with periodontitis. The results of this adaptive immune response are noted both locally and systemically with antigenic specificity for an array of oral bacteria, including periodontopathic species, e.g., Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. It has been recognized through epidemiological studies and clinical observations that the prevalence of periodontitis increases with age. This report describes our studies evaluating gingival tissue transcriptomes in humans and specifically exploiting the use of a non-human primate model of naturally occurring periodontitis to delineate gingival mucosal tissue gene expression profiles focusing on cells/genes critical for the development of humoral adaptive immune responses. Patterns of B cell and plasmacyte genes were altered in aging healthy gingival tissues. Substantial increases in a large number of genes reflecting antigen-dependent activation, B cell activation, B cell proliferation, and B cell differentiation/maturation were observed in periodontitis in adults and aged animals. Finally, evaluation of the relationship of these gene expression patterns with those of various tissue destructive molecules (MMP2, MMP9, CTSK, TNFα, and RANKL) showed a greater frequency of positive correlations in healthy tissues versus periodontitis tissues, with only MMP9 correlations similar between the two tissue types. These results are consistent with B cell response activities in healthy tissues potentially contributing to muting the effects of the tissue destructive biomolecules, whereas with periodontitis this relationship is adversely affected and enabling a progression of tissue destructive events.

Periodontal disease susceptible matrilines in the Cayo Santiago Macaca mulatta macaques

“…Table provides a summary that links the multigenerational data derived from the skulls within the matrilines to the presentation of naturally‐occurring periodontitis in living descendants of these families. The findings represent results from animals who were randomly selected and periodontal disease evaluated for participation in ongoing studies of aging effects on periodontitis and mucosal immune responses . Within the three matrilines demonstrating the least periodontal disease in the skulls, few living animals showed any naturally‐occurring disease, with <30% presenting with any disease even >10 years of age (~35 human years).…”

Ageing effects on humoral immune responses in chronic periodontitis

“…These reports described targeted mechanisms of innate immunity that are altered with aging (Hajishengallis, 2010, Hajishengallis, 2014), including various critical transcription factors and the resulting genes regulated by these factors (Chung et al, 2011). Additionally, limited studies in animal models provide evidence for increased bone loss (Liang et al, 2010), altered dendritic cell functions in response to bacterial infections (Wu et al, 2016), and substantial effects on the biology of B cell functions in the oral cavity (Ebersole et al, 2016b) that would be considered to contribute to adaptive immune effects in the aging oral cavity. These data were accompanied by identification of an altered microbial challenge that likely also contributes to an adverse response profile (Feres et al, 2016, Wu et al, 2016).…”

Microbiome diurnal rhythmicity and its impact on host physiology and disease risk

“…The diurnally changing microbiome and its impact on the host may influence other microbiome‐associated physiological states and diseases. For example, aging is associated with distinct changes in the gut microbiome . Moreover, the microbiome has been implicated to modulate various aspects of aging including longevity , and very old individuals were found to feature a microbiota composition enriched for “health‐promoting” commensals .…”

“…Moreover, the microbiome has been implicated to modulate various aspects of aging including longevity , and very old individuals were found to feature a microbiota composition enriched for “health‐promoting” commensals . While the microbiota is relatively stable in adulthood , the aging process is associated with a change in an individual's microbiome composition, which is thought to be mainly driven by environmental effects such as the use of antibiotics, changes in nutrition, and the development of chronic illnesses, including metabolic syndrome and inflammatory diseases . The microbial diversity decreases significantly with age , while the inter‐individual variability in microbiota increases significantly in elderly compared to younger adults .…”