Capsular‐defective Porphyromonas gingivalis mutant strains induce less alveolar bone resorption than W50 wild‐type strain due to a decreased Th1/Th17 immune response and less osteoclast activity

Abstract

Background Encapsulation of Porphyromonas gingivalis has been demonstrated as responsible of several host immunological changes, which have been associated with the pathogenesis of periodontitis. Using a murine model of periodontitis and two isogenic non‐capsulated mutants of P. gingivalis, this study aimed to analyze whether P. gingivalis encapsulation induces more severe alveolar bone resorption, and whether this bone loss is associated with a T‐helper (Th)1 and Th17‐pattern of immune response. Methods Experimental periodontal infections were generated by oral inoculation with the encapsulated W50 wild‐type strain or isogenic non‐encapsulated ΔPG0116‐PG0120 (GPA) and ΔPG0109‐PG0118 (GPC) mutants of P. gingivalis. Periodontal infections induced with the encapsulated HG184 or non‐encapsulated ATCC 33277 strains of P. gingivalis were used as controls. Alveolar bone resorption was analyzed using microcomputed tomography and scanning electron microscopy. The expression levels of Th1, Th2, Th17, or T regulatory‐associated cytokines and RANKL, as well as the periodontal bacterial load, were quantified by quantitative polymerase chain reaction. The detection of Th1 and Th17 lymphocytes was analyzed by flow cytometry. Results In the periodontal lesions, both capsular‐defective knockout mutant strains of P. gingivalis induced less alveolar bone resorption than the encapsulated W50 wild‐type strain. This decreased bone loss was associated with a dismissed RANKL expression, decreased Th1‐ and Th17‐type of cytokine expression, reduced Th1 and Th17 lymphocyte detection, and low osteoclast finding. Conclusion These data demonstrate that encapsulation of P. gingivalis plays a key role in the alveolar bone resorption induced during periodontitis, and this bone loss is associated with a Th1‐ and Th17‐pattern of immune response triggered in the periodontal lesions.

Alzheimer’s Disease-Like Pathology Triggered by Porphyromonas gingivalis in Wild Type Rats Is Serotype Dependent

“…The presence of P. gingivalis was determined by quantifying the total bacterial load in serum and hippocampus. Although the identification of the bacteria in the serum has been previously reported (10), the presence of all P. gingivalis serotypes in the brain is the most intriguing and novel finding of our work. After 55 days, all P. gingivalis strains were detected in both samples, demonstrating that it is possible to detect P. gingivalis in the brain, regardless of the capsule and its virulence.…”

“…The immunogenic role of P. gingivalis capsule has been previously demonstrated, and the structural variability of its polysaccharide component has been directly associated with its virulence potential (6)(7)(8)(9)(10)74). Several encapsulated and nonencapsulated (K1-K7) serotypes of P. gingivalis have been described; among them, the encapsulated serotypes display more virulence in experimental infections (10,72,75,76). Also, a P. gingivalis K1-isogenic non-encapsulated knock-out mutant DPG0116-PG0120 (GPA) has been developed, allowing to test the effects of the absence of capsule (14).…”

“…Although all these studies demonstrate, to a greater or lesser extent, that cognitive deterioration is associated with periodontitis, it remains to be elucidated whether these effects are a consequence of some periodontitis molecular mediator, the direct activity of the bacteria, general sepsis, or alteration of the intestinal microbiota, based on direct interaction between periodontal and gut microbiota. Accordingly, to identify the role of a bacterium or virulence factor in periodontitis, the model we chose was the palatal inoculation, which has been previously used by our research group in mice and known by causing an increased Th1/Th17 immune response, osteoclast activity, and alveolar bone resorption (10,44).…”

“…Without detriment to other virulence factors that P. gingivalis possesses, the capsular polysaccharides or K-antigens, which constitute the main macromolecule of its surface, are responsible for its serotypification, defining the taxonomic classification and contributing to the virulence (72,73). The immunogenic role of P. gingivalis capsule has been previously demonstrated, and the structural variability of its polysaccharide component has been directly associated with its virulence potential (6)(7)(8)(9)(10)74). Several encapsulated and nonencapsulated (K1-K7) serotypes of P. gingivalis have been described; among them, the encapsulated serotypes display more virulence in experimental infections (10,72,75,76).…”

Interleukin‐35 inhibits alveolar bone resorption by modulating the Th17/Treg imbalance during periodontitis

“…The presence of Th17 and Treg lymphocytes within the periodontal lesions and cervical lymph nodes that drain these periodontal lesions was analysed by flow cytometry, as previously described (Monasterio, Budini, et al, 2019; Monasterio, Fernandez, et al, 2019). Cells were isolated from the palatal periodontal tissue samples using procedures previously described (Pandiyan, Bhaskaran, Zhang, & Weinberg, 2014; Vernal et al, 2005).…”