Osteoimmunology As A New Frontier in Treponemal Infection

University Of Louisville Research Foundation Inc, Louisville KY

Investigators

Abstract

Dr. Fabian Crespo together with colleagues will undertake research to test the potential for integrating experimental osteoimmunology with bioarchaeology in reconstructing human host immune response and inflammatory phenotype (IP) focusing on immune responses against acquired syphilis's causal bacterium, Treponema pallidum; and ultimately explore how changes in inflammatory responses impact bone cell physiology. This project represents an experimental immunological complement to a more traditional bioarchaeological analysis (PI: Zuckerman), wherein host IP during the stages of infection will be reconstructed through biomarkers of other inflammatory conditions, specifically periodontal disease (PD). This project will establish the potential immunological interplay between systemic inflammatory responses against T. pallidum and other pathogens, such Porphyromonas gingivalis, which is causal to PD, and how this interplay may influence localized bone microenvironments, enabling skeletal biomarkers, such as PD, to be used to reconstruct IP with empirical certainty. Dr. Crespo and colleagues are committed to giving multiple public and K-12 lectures in collaboration with local and national educational organizations regarding health and social consequences of sexually transmitted infections (STIs), such as syphilis; and ultimately, emphasizing how the integration of skeletal analyses of disease in past populations, through bioarchaeology, with modern biomedical analysis, through osteoimmunology, can transform current understandings of human health. Dr. Crespo and colleagues will try to answer the following research questions: (1) Does exposing human immune cells to T. pallidum induce a systemic inflammatory shift that affects the host immune response to P. gingivalis; (2) Does exposing immune cells to P. gingivalis induce a shift that affects the host immune response to T. pallidum? (3) Does this potential shift have downstream effects on localized bone microenvironments, affecting bone cell differentiation and activity? (4) Lastly, can the potential inflammatory shift and physiological changes observed in vitro be associated with PD in skeletons with documented T. pallidum infection? These questions will be answered using peripheral blood mononuclear cells (PBMCs) from healthy donors, splitting the cell population in two groups: a) whole PBMCs to explore evidence for an inflammatory shift when cells are alternatively exposed to antigens and lysates from T. pallidum and P. gingivalis; and b) isolated CD14+ monocytes, which differentiate into bone cells, from PBMCs (same donor), to assess how the potential shift might affect bone cell differentiation and activity. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.