Osteoimmunology As A New Frontier in Treponemal Infection

Fabian Crespo博士及其同事将进行研究，以测试将实验性骨免疫学与生物考古学相结合的潜力，重建人类宿主免疫反应和炎症表型（IP），重点关注对获得性梅毒致病菌梅毒螺旋体的免疫反应;并最终探索炎症反应的变化如何影响骨细胞生理学。该项目代表了对更传统的生物考古学分析（PI：Zuckerman）的实验免疫学补充，其中感染阶段的宿主IP将通过其他炎症条件的生物标志物重建，特别是牙周病（PD）。本项目将建立潜在的免疫相互作用的全身炎症反应对T。苍白球和其他病原体，如牙龈卟啉单胞菌，这是导致PD，以及这种相互作用如何可能影响局部骨微环境，使骨骼生物标志物，如PD，用于重建IP与经验的确定性。Crespo博士及其同事致力于与地方和国家教育组织合作，就性传播感染（STI）的健康和社会后果（如梅毒）进行多次公开和K-12讲座;最后，强调如何通过生物考古学，结合现代生物医学分析，通过骨免疫学，可以改变目前对人类健康的理解。Crespo博士和他的同事们将试图回答以下研究问题：（1）将人类免疫细胞暴露于T。苍白球诱导影响宿主对牙龈卟啉单胞菌的免疫应答的全身性炎症转变;（2）将免疫细胞暴露于牙龈卟啉单胞菌是否诱导影响宿主对T.苍白球？(3)这种潜在的转变是否对局部骨微环境产生下游效应，影响骨细胞分化和活性？(4)最后，在体外观察到的潜在炎症转移和生理变化是否与有记录的T。苍白球感染这些问题将使用来自健康供体的外周血单核细胞（PBMC）来回答，将细胞群体分成两组：a）全PBMC以探索当细胞交替暴露于抗原和来自T的裂解物时炎性转变的证据。苍白球和牙龈卟啉单胞菌;和B）从PBMC（同一捐赠者）分离的分化成骨细胞的CD 14+单核细胞，以评估潜在的转变如何影响骨细胞分化和活性。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.