Estudo da relação entre a infecção pelo vírus Chikungunya e a doença periodontal experimental induzida em camundongos

Abstract

The Chikungunya virus (CHIKV) belongs to the genus Alphavirus, of the Togaviridae family and has a single-stranded RNA genome of positive polarity. Studies show that microorganisms such as CHIKV can be associated with arthritogenic conditions, leading to symptoms such as pain and joint stiffness. CHIKV infection causes systemic involvement, and oral changes such as bleeding and alveolar bone loss can also be observed, resulting in dental instability, which are characteristics of periodontal disease (PD). PD is an inflammatory disease of infectious etiology that can affect the gums, alveolar bone, and periodontal ligament. Furthermore, maintaining the periodontal inflammatory process can induce the translocation of bacteria from the oral cavity to extraoral sites, linking PD to different pathological processes including rheumatoid arthritis (RA). Although PD is considered important in the pathogenesis of RA, the relationship between PD and arthritogenic conditions such as those caused by CHIKV still requires further clarification. Thus, this study aimed to evaluate the mechanisms involved in periodontal changes associated with CHIKV infection in mice. For this purpose, C57BL/6 mice were inoculated with 1 x 106 PFU/mL of CHIKV in the right footpad. After euthanasia, periodontal tissues were collected at different experimental time points for analysis of alveolar bone loss, histopathology and evaluation of the production of inflammatory mediators. Our results show that intraplantar CHIKV infection has induced alveolar bone resorption, which was associated with an increased number of osteoclasts in the alveolar bone crest of mice. However, this alveolar bone loss was not related to CHIKV-induced osteoclastogenesis, as it was observed that CHIKV did not induce the formation of osteoclasts, as CHIKV did not directly stimulate osteoclast formation. Therefore, our results show that the CHIKV-induced alveolar bone loss depends on periodontal inflammation, since an increased production of inflammatory mediators was observed, such as CCL2, IFNγ, RANKL and IL-6, along with reduced OPG production at later times and an imbalance in the RANKL:OPG ratio. Furthermore, gingival fibroblasts produced IL-6 when infected with CHIKV and, in the absence of IL-6, CHIKV-infected mice did not show alveolar bone loss. Changes in the oral microbiota induced by CHIKV were also observed, and no alveolar bone loss was observed in germ-free mice or mice treated with chlorhexidine (CHX), highlighting the critical role of the oral microbiota in this context. In conclusion, intraplantar CHIKV infection is associated with the induction of periodontal inflammation, changes in the oral microbiota, which, in turn, lead to an imbalance in the RANKL:OPG ratio, culminating in increased amount of osteoclasts in the alveolar bone crest and induction of alveolar bone loss.