Macrophage polarization in peri-implantitis lesions

Abstract

Objectives To immunohistochemically characterize and correlate macrophage M1/M2 polarization status with disease severity at peri-implantitis sites. Materials and methods A total of twenty patients (n = 20 implants) diagnosed with peri-implantitis (i.e., bleeding on probing with or without suppuration, probing depths ≥ 6 mm, and radiographic marginal bone loss ≥ 3 mm) were included. The severity of peri-implantitis was classified according to established criteria (i.e., slight, moderate, and advanced). Granulation tissue biopsies were obtained during surgical therapy and prepared for immunohistological assessment and macrophage polarization characterization. Macrophages, M1, and M2 phenotypes were identified through immunohistochemical markers (i.e., CD68, CD80, and CD206) and quantified through histomorphometrical analyses. Results Macrophages exhibiting a positive CD68 expression occupied a mean proportion of 14.36% (95% CI 11.4-17.2) of the inflammatory connective tissue (ICT) area. Positive M1 (CD80) and M2 (CD206) macrophages occupied a mean value of 7.07% (95% CI 5.9-9.4) and 5.22% (95% CI 3.8-6.6) of the ICT, respectively. The mean M1/M2 ratio was 1.56 (95% CI 1-12-1.9). Advanced peri-implantitis cases expressed a significantly higher M1 (%) when compared with M2 (%) expression. There was a significant correlation between CD68 (%) and M1 (%) expression and probing depth (PD) values. Conclusion The present immunohistochemical analysis suggests that macrophages constitute a considerable proportion of the inflammatory cellular composition at peri-implantitis sites, revealing a significant higher expression for M1 inflammatory phenotype at advanced peri-implantitis sites, which could possibly play a critical role in disease progression. Clinical relevance Macrophages have critical functions to establish homeostasis and disease. Bacteria might induce oral dysbiosis unbalancing the host's immunological response and triggering inflammation around dental implants. M1/M2 status could possibly reveal peri-implantitis' underlying pathogenesis.

Pharyngeal spreading of peri-implant infections under antiresorptive/antiangiogenic therapy

“…When further analyzing the characteristics of the ICTs, it was observed that they were dominated by CD68positive cells, lymphocytes, polymorphonuclear leukocytes, and plasma cells. Basically, these characteristics closely resemble those commonly noted for mixed inflammatory cell infiltrates in peri-implantitis lesions [2,3,[20][21][22][23]. As opposed to periodontitis lesions, the inflammatory lesions at implant sites were reported to be larger in size and associated with higher proportions of macrophages [2,24].…”

“…As opposed to periodontitis lesions, the inflammatory lesions at implant sites were reported to be larger in size and associated with higher proportions of macrophages [2,24]. Due to their potential relevance in the pathogenesis of peri-implant diseases [20], the present analysis had a major focus on the assessment of CD68-positive cells. In this context, it must also be emphasized that peri-implantitis lesions were characterized by an increase in the density of vascular structures [2], and that a marked portion of associated inflammatory cells were also present in peri-vascular compartments [3].…”

Characterization of Macrophages and TNF-α in Cleft Affected Lip Tissue

“…Even though we observed a simultaneous increase in both factors, many studies have proven that different M1 and M2 appearance patterns also exist. For instance, M1 dominance has been observed not only in periodontitis [32] but also at advanced peri-implantitis sites [33]. In a COPD mouse model, alveolar macrophages favoured the M2 phenotype, thus skewing the macrophage ratio in favour of M2 [34].…”

Macrophagic Inflammatory Response Next to Dental Implants with Different Macro- and Micro-Structure: An In Vitro Study

“…A recent clinical study investigated the inflammatory cell infiltrate at implants affected by peri-implantitis [15]. They found higher expression of M1 pro-inflammatory macrophages and subsequently an increased M1/M2 ratio, particularly at advanced periimplantitis cases.…”

“…They found higher expression of M1 pro-inflammatory macrophages and subsequently an increased M1/M2 ratio, particularly at advanced periimplantitis cases. In addition, a significant correlation was found between M1 expression and probing depth (PD) values [15].…”