Effects of Age and Oral Disease on Systemic Inflammatory and Immune Parameters in Nonhuman Primates

Abstract

This report evaluated systemic inflammatory and immune biomarkers in a cohort of Macaca mulatta (rhesus monkeys) maintained as a large family social unit, including an age range from <1 year to >24 years. We hypothesized that the systemic host responses would be affected by the age, gender, and clinical oral presentation of the population, each contributing to inflammatory and immune responses that would reflect chronic oral infections. The results demonstrated that the prevalence and severity of periodontitis, including missing teeth, increased significantly with age. Generally, minimal differences in clinical parameters were noted between the genders. Systemic inflammatory mediators, including acute-phase reactants, prostaglandin E 2 (PGE 2 ), cytokines/chemokines, and selected matrix metalloproteinases (MMP), demonstrated significant differences among the various age groups of animals. Levels of many of these were increased with age, although PGE 2 , RANTES, bactericidal permeability-inducing factor (BPI), MMP-1, and MMP-9 levels were significantly increased in the young group (ϳ1 to 3 years old) relative to those for the older animals. We observed that in the adult and aged animals, levels of the systemic inflammatory mediators related to gingival inflammation and periodontal tissue destruction were significantly elevated. Serum antibody levels in response to a battery of periodontal pathogens were generally lower in the young animals, <50% of those in the adults, and were significantly related to aging in the cohort. The levels of antibodies, particularly those to Porphorymonas gingivalis, Fusobacterium nucleatum, and Tannerella forsythia, were most significantly elevated in animals with periodontal disease, irrespective of the age of the animal. These results provide a broad description of oral health and host responses in a large cohort of nonhuman primates from very young animals to the aged of this species. The findings afford a base of data with which to examine the ontogeny of host responses at mucosal sites, such as the gingival tissues.Periodontal disease is the predominant chronic inflammatory disease of humanity (37,38,78,82) and has been noted to occur naturally with increasing age in humans and nonhuman primates (36,63,69,88). This oral disease is an outcome of complex oral infections, chronic immunoinflammatory responses, and resulting destruction of soft and hard tissues of the periodontium (37,78,80,82,84). In both humans and nonhuman primates, the extent of disease is predicted to be controlled by the quality and quantity of the host response and likely is modulated by systemic disease (48), environmental stressors (6, 76, 85), and the genetic backgrounds of the individuals (3, 70, 84).The oral microbial characteristics of subgingival biofilms in younger and older individuals demonstrate differences in composition and complexity, which have been suggested to contribute directly to the microbial infections that trigger the destructive disease of oral tissues that occurs during aging (4,35,49,...

Apoptotic Genes are Differentially Expressed in Aged Gingival Tissue

“…The clinical examination included probing pocket depth (PD) and bleeding on probing (BOP; 0-3 scale) (Ebersole et al, 2008). Clinical characterization for each group Genes shown in red are over-expressed, and genes shown in yellow are under-expressed in young gingival tissue compared with aged gingival tissue.…”

“…Consistent with age being a modifier for the prevalence or severity of periodontal disease, important biological differences in the composition and complexity of the oral microbial ecology, as well as the oral/systemic immune-inflammatory responses during aging, have been described in humans and animal models (Schlegel-Bregenzer et al, 1998;Nonnenmacher et al, 2001;Ebersole et al, 2008). Paradoxically, the reduced immunity in aging is accompanied by chronic inflammation (Back et al, 2007), which may reflect a perturbation of the innate immune mechanisms associated with age (Agrawal et al, 2007).…”

Acquisition of Oral Microbes and Associated Systemic Responses of Newborn Nonhuman Primates

“…Biological changes in response to this chronic polymicrobial infection can be measured in the local periodontal environment, as well as systemically (26,38,39). Evidence from oral infections related to dental caries has demonstrated that young humans are infected early in life with Streptococcus mutans, generally contracted from the primary caregiver (40,41).…”

Gene Regulation, Two Component Regulatory Systems, and Adaptive Responses in Treponema Denticola

“…Signature species differences in the composition of the bacterial population at specific niches have been demonstrated and shown to correlate with infections including caries, endodontic infections, gingivitis, subgingival plaque and periodontitis (Siqueira and Rocas 2004;Zijnge et al 2010). The composition of the oral bacterial community varies significantly among individuals and changes with age, diet, hygiene, anatomical niche, health status, and other factors (Darveau 2010;Ebersole et al 2008). As periodontal disease progresses, significant changes occur in the physiochemical and immunological environment of the gingival sulcus or subgingival crevice (the space between the tooth and gum tissue) (reviewed in McDowell et al 2012).…”