O papel dos receptores FcγRIIb e FCγRIII na reabsorção óssea alveolar experimental

Abstract

Bone resorption diseases, such as Periodontal Disease (PD), are characterized by an imbalance between bone matrix production and resorption. PD, an inflammatory disease with an infectious etiology, can lead to the resorption of alveolar bone. Despite the recognized role of the immune response in PD development, little is known about the involvement of IgG and its receptors in this context. Thus, this study aimed to assess the contribution of Fc𝛾RIIb and Fc𝛾RIII in PD pathogenesis. For this, wild-type (WT) or deficient C57BL6 mice (Mu-/-, Fcgr2b-/- or Fcgr3-/-) were infected with 100 μL of 1 x 109 CFU/mL of Aggregatibacter actinomycetemcomitans (Aa - ATCC 43718) solution, in PBS, with 1.5% carboxymethyl cellulose (CMC), via oral inoculation. Sham-infected mice received a placebo solution with 100 μL of PBS with 1.5% CMC, in the oral cavity. The inoculation was repeated three times, with 48-hour intervals, 30 days before euthanasia (CEUA 153/2022). WT mice exhibited alveolar bone loss (ABL) and an increased osteoclasts numbers, in response to Aa infection. In contrast, Mu-/- or Fcgr2b-/- mice did not develop ABL upon infection, although Mu-/- mice showed bacterial translocation to the liver. Fcgr2b-/- control mice, when compared to WT controls, displayed higher neutrophil counts and increased CXCL1 and IL-1β production in periodontal tissues. While an increased levels of IL-1β, IL-17, RANKL, and MPO, and a greater number of neutrophils were observed in Aa-induced WT animals, it was not presented by infected Fcgr2b-/- mice. Therefore, these factors may have contributed to the impaired ABL or bacterial translocation to the liver in Fcgr2b-/- mice. Interestingly, uninfected Fcgr3-/- showed changes in the alveolar bone compared to uninfected WT mice, although both WT and Fcgr3-/- mice developed Aa-induced ABL. Furthermore, uninfected Fcgr3-/- mice displayed higher levels of anti-Aa IgG and increased IgG deposition in the maxilla. Analysis of the oral microbiota in uninfected mice revealed greater microbial diversity in Fcgr3-/- mice compared to WT mice. Overall, these findings suggest that Fc𝛾RIII plays a crucial role in controlling the oral microbiota and, consequently, ABL.