MAXILLOFACIAL INFECTION: FOCUS ON PERIODONTAL DISEASE

Di Emidio P, Cardinelli D. Maxillofacial infection: focus on periodontal disease. International Journal of Infection. 2024;8(1):14-17.

P. Di Emidio^* and D. Cardinelli

Department of maxillofacial surgery and odontostomatology, “G. Mazzini” Hospital, Teramo, Italy.

*Correspondence to:
Dr. Paolo Di Emidio,
Department of maxillofacial surgery and odontostomatology,
“G. Mazzini” Hospital,
Teramo, Italy.
e-mail: paolo.diemidio@aslteramo.it

Received: 19 January, 2024 Accepted: 29 February, 2024

ISSN 1972-6945 [online] Copyright 2024 © by Biolife-publisher This publication and/or article is for individual use only and may not be further reproduced without written permission from the copyright holder. Unauthorized reproduction may result in financial and other penalties. Disclosure: all authors report no conflicts of interest relevant to this article.

ABSTRACT

Craniofacial structures, such as the mouth, teeth, and gums, can be subject to both acute and chronic infections. Management of maxillofacial infections, which activate immunity and inflammation, is very important since they can lead to serious complications. The most common pathogens responsible for these infection are viruses, bacteria, and fungi. Maxillofacial infections can be odontogenic, including dental abscesses, jawbone abscesses, and periodontitis, amongst others, and activate the immune system, generating inflammatory molecules. Lipopolysaccharide (LPS) present in Gram-negative bacteria is a large molecule capable of activating immunity and inflammation in the oropharygeal system. Bacterial infections, especially those mediated by Gram-negative bacteria, can cause periodontitis, where the immune response is triggered, resulting in chronic inflammation with gingival damage. Immune molecules, including metalloproteinases (MMPs) and cytokines, such as interleuking (IL)-1, tumor necrosis factor (TNF), and IL-6, are released and mediate inflammation and tissue damage. Upon stimulation, osteoclasts, the precursors of macrophages, lead to the activation of the receptor for nuclear factor kappa B (NF-kB), receptor activator of nuclear factor κ B-ligand (RANKL), and other proteins that contribute to osteoclastogenesis and therefore, bone loss. It can be concluded that bacterial infections can mediate periodontitis in chronic and severe cases.

KEYWORDS: Infection, maxillofacial, periodontitis, immunity, inflammation, bacteria

INTRODUCTION

Chronic infections can contribute to local and systemic inflammation and increase the risk of various disorders, including craniofacial diseases affecting the mouth, teeth, and gums (1). Maxillofacial infections involve the facial bones and soft tissues and can lead to significant complications if not properly managed (2). Understanding the mechanisms of infection, inflammation, and immunity in the maxillofacial region is crucial for effective treatment.

Infections begin with pathogens entering the oral mucosa, dental caries, or through spaces created by trauma (3). Infections can affect the face, lymphatic system, or bloodstream (4). The most common pathogens which are responsible for these infections include bacteria (such as Staphylococcus aureus and some species of Streptococcus), viruses (such as herpes simplex), and fungi (such as Candida) (5).

DISCUSSION

Typical maxillofacial infections are odontogenic infections originating from dental structures (for example, dental abscesses) (6), but also from soft tissue infections such as cellulitis and abscesses, as well as infections of the jaw bones (osteomyelitis) (7). Neutrophils and macrophages are innate immune cells that constitute a physical barrier of the tissues and are the first immune cells that intervene in infections for the recognition of pathogens (8). Adaptive immunity involves the intervention of B cells that produce antibodies to try to neutralize the pathogen and facilitate its elimination (9). Helper T cells and cytotoxic T cells are part of cell-mediated immunity and target and kill infected cells, orchestrating the immune response (10). Pathogens defend themselves from the immune process by forming biofilms to resist phagocytosis and antibiotic treatment and can alter host immune responses to evade detection and destruction (11).

Tissue inflammation can be activated by bacterial products such as lipopolysaccharide (LPS) (12). LPS is a large molecule found in the outer membrane of Gram-negative bacteria that plays a key role in the development of inflammation. LPS triggers the immune response in the host by acting as an endotoxin. It causes inflammation and tissue damage, and stimulates the production of cytokines, prostaglandins, and other mediators involved in bone resorption. In addition, LPS can contribute to the progression of periodontitis (13).

Periodontal disease

Periodontitis is a gum infection that damages the soft tissue and can be serious (14). Bacteria are primarily responsible for causing this disease (15). Periodontitis is a chronic infection that occurs in 50% of the adult population in industrialized countries. Bacteria, particularly Gram-negative bacteria containing LPS, proliferate and release LPS, which triggers an immune response, causing chronic inflammation damages gum tissue and bone, which ultimately results in tooth loss if the infection is not treated (16).

In the mouth, certain bacteria can form plaque on the teeth that, if not removed, forms tartar which continues to host the bacteria (17). These bacteria stimulate molecules that attract immune cells and cause inflammation of the gums, i.e. gingivitis, the stage which occurs before periodontitis (18). Gingivitis is commonly caused by poor oral hygiene and leads to the accumulation of bacterial plaque on the gums that, without proper treatment, can destroy the bone that supports the teeth. In this disease, inflammatory molecules such as metalloproteinases (MMPs) are activated, along with others, and enter the inflammatory cascade (19). MMPs participate in the recruitment of migratory immune cells to the inflammatory site (20).

Several lines of experimental and clinical evidence indicate that inflammation in periodontal disease leads to bone loss (21). Periodontal disease is mediated by bacterial antigens that cause the activation of the immune system and inflammatory reactions. The first reaction is the activation of innate immunity with the generation of inflammatory cytokines and arachidonic acid products due to the activation of monocytes/macrophages, dendritic cells, and mast cells (22). The most important inflammatory cytokines that are secreted by the immune reaction are interleukin (IL)-1, tumor necrosis factor (TNF), and IL-6 (23). T and B lymphocytes stimulated by the antigen also activate the adaptive immune response and participate in the inflammatory reaction (24). In these reactions, which stimulate the differentiation of macrophage precursor cells into osteoclasts, there is activation of the receptor for nuclear factor kappa B (RANK) -ligand (RANKL) and other proteins that lead to osteoclastogenesis and thus bone loss (25). Therefore, stimulation of osteoclast maturation leads to bone loss. On osteoclast progenitors, inflammatory cytokines and other proteins participate in bone resorption and act through the RANK to RANKL binding reaction (26). Therefore, RANKL is critical for regulating bone metabolism.

To prevent periodontitis, proper dental hygiene is crucial to avoid the buildup of plaque, and when necessary, antibiotic therapy is important to eliminate bacteria (27). In addition, severe cases of periodontitis may require surgery to clean deeply infected pockets and repair damaged tissue (28).

CONCLUSIONS

Infectious diseases caused by bacteria are treated with antibiotics specifically selected based on the involved pathogens. Surgical interventions are also very common for drainage of abscesses, removal of necrotic tissue, and management of the source of infection. Anti-inflammatory drugs are used against pain and swelling.

In maxillofacial infections, there are complex interactions between pathogens, host immune responses, and inflammatory processes. These reactions are still not fully elucidated and continued research is vital to shed light on mechanisms which could help generate new effective treatment strategies to manage infections and prevent disease. Understanding the role of bacteria in periodontitis is important to prevent the onset and progression of this oral disease.

Conflict of interest

The authors declare that they have no conflict of interest.

REFERENCES

1. Break TJ, Oikonomou V, Dutzan N, et al. Aberrant type 1 immunity drives susceptibility to mucosal fungal infections. Science. 2021;371(6526). doi:https://doi.org/10.1126/science.aay5731
2. Chkadua TZ, Oltarzhevskaya ND, Cholokava TD, Baisova LM, Sogachev GV, Egiazaryan AK. Post-Covid osteomyelitis of the facial bones. Stomatology. 2023;102(6):68-68. doi:https://doi.org/10.17116/stomat202310206268
3. Pedersen AML, Sørensen CE, Proctor GB, Carpenter GH, Ekström J. Salivary secretion in health and disease. Journal of Oral Rehabilitation. 2018;45(9):730-746. doi:https://doi.org/10.1111/joor.12664
4. Gendron R, Grenier D, Maheu-Robert LF. The oral cavity as a reservoir of bacterial pathogens for focal infections. Microbes and Infection. 2000;2(8):897-906. doi:https://doi.org/10.1016/s1286-4579(00)00391-9
5. Wertheim HF, Melles DC, Vos MC, et al. The role of nasal carriage in Staphylococcus aureus infections. The Lancet Infectious Diseases. 2005;5(12):751-762. doi:https://doi.org/10.1016/s1473-3099(05)70295-4
6. Ogle OE. Odontogenic Infections. Dental Clinics of North America. 2017;61(2):235-252. doi:https://doi.org/10.1016/j.cden.2016.11.004
7. Calhoun KH, Shapiro R, Stiernberg CM, Calhoun JH, Mader JT. Osteomyelitis of the Mandible. Archives of otolaryngology–head & neck surgery. 1988;114(10):1157-1162. doi:https://doi.org/10.1001/archotol.1988.01860220091031
8. Murakami Y, Hanazawa S, Tanaka S, Iwahashi H, Yamamoto Y, Fujisawa S. A possible mechanism of maxillofacial abscess formation: involvement of Porphyromonas endodontalis lipopolysaccharide via the expression of inflammatory cytokines. Oral Microbiology and Immunology. 2001;16(6):321-325. doi:https://doi.org/10.1034/j.1399-302x.2001.160601.x
9. Klitynska OV, Roksolana Yu. Kruchak, Gurando VR, Shetelya VV, Layoch NV, Mochalov IO. Immunity changes in patients with acute maxillofacial odontogenic infections during treatment stages: an analysis. Wiadomości Lekarskie. 2023;76(11):2442-2447. doi:https://doi.org/10.36740/wlek202311116
10. Dumitrescu A, Martu MA, Nemtoi A, et al. Association between Cone-Beam Computed Tomography and Histological and Immunohistochemical Features in Periapical Lesions Correlated with Thickened Maxillary Sinus Mucosa. Medicina. 2021;57(8):840. doi:https://doi.org/10.3390/medicina57080840
11. López-Píriz R, Aguilar L, Giménez MJ. Management of odontogenic infection of pulpal and periodontal origin. Medicina oral, patología oral y cirugía bucal. 2007;12(2):E154-E159.
12. Pei F, Lin H, Liu H, Li L, Zhang L, Chen Z. Dual Role of Autophagy in Lipopolysaccharide-induced Preodontoblastic Cells. Journal of Dental Research. 2014;94(1):175-182. doi:https://doi.org/10.1177/0022034514553815
13. Wiebe S, Hafezi M, Sandhu H, Sims S, Dixon S. Osteoclast activation in inflammatory periodontal diseases. Oral Diseases. 2008;2(2):167-180. doi:https://doi.org/10.1111/j.1601-0825.1996.tb00218.x
14. Hitz Lindenmüller I, Lambrecht JT. Oral care. Current Problems in Dermatology. 2011;40:107-115. doi:https://doi.org/10.1159/000321060
15. Langendijk PS, Hanssen JTJ, Van der Hoeven JS. Sulfate-reducing bacteria in association with human periodontitis. Journal of Clinical Periodontology. 2000;27(12):943-950. doi:https://doi.org/10.1034/j.1600-051x.2000.027012943.x
16. Li Z, Cai Q, Li B, Meng W. Caspase-11/4 is involved in bacteria-mediated periodontitis by promoting the release of interleukin-1 β and tumor necrosis factor-α. Archives of Oral Biology. 2022;142:105517-105517. doi:https://doi.org/10.1016/j.archoralbio.2022.105517
17. Arweiler NB, Netuschil L. The Oral Microbiota. Microbiota of the Human Body. 2016;902:45-60. doi:https://doi.org/10.1007/978-3-319-31248-4_4
18. Page RC. Gingivitis. Journal of Clinical Periodontology. 1986;13(5):345-355. doi:https://doi.org/10.1111/j.1600-051x.1986.tb01471.x
19. Luchian I, Goriuc A, Sandu D, Covasa M. The Role of Matrix Metalloproteinases (MMP-8, MMP-9, MMP-13) in Periodontal and Peri-Implant Pathological Processes. International Journal of Molecular Sciences. 2022;23(3):1806. doi:https://doi.org/10.3390/ijms23031806
20. Zhang H, Liu L, Jiang C, Pan K, Deng J, Wan C. MMP9 protects against LPS-induced inflammation in osteoblasts. Innate Immunity. 2019;26(4):259-269. doi:https://doi.org/10.1177/1753425919887236
21. Hienz SA, Paliwal S, Ivanovski S. Mechanisms of Bone Resorption in Periodontitis. Journal of Immunology Research. 2015;2015:1-10. doi:https://doi.org/10.1155/2015/615486
22. Rakhi Sinha Morton, Dongari-Bagtzoglou A. Cyclooxygenase-2 Is Upregulated in Inflamed Gingival Tissues. Journal of Periodontology. 2001;72(4):461-469. doi:https://doi.org/10.1902/jop.2001.72.4.461
23. Ghassib I, Chen Z, Zhu J, Wang HL. Use of IL-1 β, IL-6, TNF-α, and MMP-8 biomarkers to distinguish peri-implant diseases: A systematic review and meta-analysis. Clinical Implant Dentistry and Related Research. 2018;21(1):190-207. doi:https://doi.org/10.1111/cid.12694
24. Zou J, Zeng Z, Xie W, Zeng Z. Immunotherapy with regulatory T and B cells in periodontitis. International Immunopharmacology. 2022;109:108797. doi:https://doi.org/10.1016/j.intimp.2022.108797
25. Wu L, Luo Z, Liu Y, et al. Aspirin inhibits RANKL-induced osteoclast differentiation in dendritic cells by suppressing NF-κB and NFATc1 activation. Stem Cell Research & Therapy. 2019;10(1):375. doi:https://doi.org/10.1186/s13287-019-1500-x
26. Kitaura H, Marahleh A, Ohori F, et al. Osteocyte-Related Cytokines Regulate Osteoclast Formation and Bone Resorption. International Journal of Molecular Sciences. 2020;21(14):5169. doi:https://doi.org/10.3390/ijms21145169
27. Kwon T, Lamster IB, Levin L. Current Concepts in the Management of Periodontitis. International Dental Journal. 2020;71(6).
28. Deas DE, Moritz AJ, Sagun RS, Gruwell SF, Powell CA. Scaling and root planing vs. conservative surgery in the treatment of chronic periodontitis. Periodontology 2000. 2016;71(1):128-139. doi:https://doi.org/10.1111/prd.12114