Differential Gene Expression Profiles Reflecting Macrophage Polarization in Aging and Periodontitis Gingival Tissues

Abstract

SUMMARY Recent evidence has determined a phenotypic and functional heterogeneity for macrophage populations. This plasticity of macrophage function has been related to specific properties of subsets (M1, M2) of these cells in inflammation, adaptive immune responses, and resolution of tissue destructive processes. This investigation hypothesized that targeted alterations in the distribution of macrophage phenotypes in aged individuals, and with periodontitis would be skewed towards M1 inflammatory macrophages in gingival tissues. The study used a nonhuman primate model to evaluate gene expression profiles as footprints of macrophage variation in healthy and periodontitis gingival tissues from animals 3–23 years of age and in periodontitis tissues in adult and aged animals. Significant increases in multiple genes reflecting overall increases in macrophage activities were observed in healthy aged tissues, and were significantly increased in periodontitis tissues from both adults and aged animals. Generally, gene expression patterns for M2 macrophages were similar in healthy young, adolescent, and adult tissues. However, modest increases were noted in healthy aged tissues, similar to those seen in periodontitis tissues from both age groups. M1 macrophage gene transcription patterns increased significantly over the age range in healthy tissues, with multiple genes (e.g. CCL13, CCL19, CCR7, TLR4) significantly increased in aged animals. Additionally, gene expression patterns for M1 macrophages were significantly increased in adult health versus periodontitis and aged healthy versus periodontitis. The findings supported a significant increase in macrophages with aging and in periodontitis. The primary increases in both healthy aged tissues and, particularly periodontitis tissues appeared in the M1 phenotype.

Proinflammatory M1 Macrophages Inhibit RANKL-Induced Osteoclastogenesis

“…Interestingly, our data suggest that M1 is the major phenotype among infiltrating macrophages in the periodontally diseased gingival tissue of experiment mice and that they suppress bone resorption by inhibiting osteoclastogenesis through their production of IL-12 and IFN-␥. Gonzalez et al showed that mixed populations of M1 and M2 are present in the periodontally diseased gingival tissue of nonhuman primates and also that the proportions of polarized macrophages change with aging (38). It was also found that gene expression patterns for M1 macrophages were significantly elevated in periodontally healthy primates compared to those seen with primates with periodontitis (38).…”

“…Gonzalez et al showed that mixed populations of M1 and M2 are present in the periodontally diseased gingival tissue of nonhuman primates and also that the proportions of polarized macrophages change with aging (38). It was also found that gene expression patterns for M1 macrophages were significantly elevated in periodontally healthy primates compared to those seen with primates with periodontitis (38). However, at this time, determination of the macrophage phenotype in periodontitis and rheumatoid arthritis in human and mouse model remains elusive.…”

Macrophage polarization in human gingival tissue in response to periodontal disease

“…It is now clear that macrophages of different phenotypes play different roles in the immune response, and temporal imbalance or the predominance of one phenotype may lead to pathological changes, including chronic inflammation and fibrosis (Biswas, Chittezhath, Shalova, & Lim, ). Thus, the proportion of pro‐inflammatory M1‐type macrophages and anti‐inflammatory M2‐type macrophages in gingival tissue presents a critical target for monitoring immune responses in subgingival biofilms as well as disease activity across the involved periodontal tissues (Gonzalez et al, ).…”

Pathogenesis of Periodontal Disease

“…In periodontal inflammation models, macrophages share properties of both M1 and M2. However, M1 macrophages show a predominance over M2 macrophages, suggesting that M1 macrophages probably represent a subset associated with periodontitis [35][36][37].…”