Date on Senior Honors Thesis

5-2023

Document Type

Senior Honors Thesis

Degree Name

B.S.

Department

Anthropology

Author's Keywords

osteoimmunology; osteoclast; treponema pallidum; oral pathogen; systemic inflammation

Abstract

Syphilitic infection caused by bacterium Treponema pallidum pallidum (Tp) offers an excellent model to study the long-lasting interplay between the immune and skeletal systems and could be used to reconstruct host immunological status. We propose that a hyper-inflammatory phenotype developed during acquired syphilis will have a systemic impact on most bone microenvironments involving inflammatory processes, such as the one developed in periodontal disease (PD). Using osteoimmunological in vitro protocols, we explore whether immune activation by Tp antigens and PD pathogens can impact osteoclastogenesis (OCG), ultimately helping to understand the bone alterations caused by systemic inflammatory processes in skeletal material. We used two main protocols, immune cell activation and osteoclastogenesis, that utilized peripheral blood mononuclear cells (PBMC’s) from healthy donors. The results showed an increased cytokine expression for IL-6, but not for TNFα, when PBMC’s were exposed to Tp antigens. OCG was affected by TNFα expression, but not IL-6 expression. Interestingly, one oral pathogen lysate, A. actinomycetemcomitans, showed different results than what was observed for the other three oral pathogen lysates. Chronic syphilis infection, through systemic inflammation, could impact bone microenvironments between seemingly unrelated forms of skeletal inflections such as syphilis and PD, and that association is influenced by the microbiome diversity observed in PD.

Lay Summary

Infection with syphilis caused by bacterium Treponema pallidum pallidum (Tp) offers an excellent model to study the long-lasting interplay between the immune and skeletal systems and could be used to reconstruct the immune status of skeletal remains. We propose that a shift toward excessive inflammation developed during acquired syphilis will have an impact on the inflammatory processes of bone, which can be observed in the context of periodontal disease (PD). We explore whether immune activation by Tp antigens and PD pathogens can impact bone growth and resorption, ultimately helping to understand the changes to bone structure caused by systemic inflammatory processes. We used two main strategies, activation of immune cells by antigens from T. pallidum and oral pathogens present in PD, and using the same cells, the generation of bone growth. The results showed that cells exposed to the T. pallidum antigen increased inflammatory responses for some oral pathogens, but not for others. Bone growth was affected by these inflammatory responses, but not consistently. Interestingly, one oral pathogen showed different results than what was observed for the other three oral pathogens. Chronic syphilis infection, through inflammation, could impact bones between seemingly unrelated forms of skeletal inflections such as syphilis and PD, and that association is influenced by the different oral pathogens observed in PD.

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