Osteoimmunology As A New Frontier in Treponemal Infection

Fabian Creso博士将与同事一起进行研究，以测试将实验骨免疫学与生物考古学相结合在重建人类宿主免疫反应和炎症表型(IP)方面的潜力，重点是针对获得性梅毒病因细菌梅毒的免疫反应；并最终探索炎症反应的变化如何影响骨细胞生理。该项目代表了对更传统的生物考古分析(PI：Zuckerman)的实验性免疫学补充，其中感染阶段的宿主IP将通过其他炎症条件的生物标记物重建，特别是牙周病(PD)。该项目将建立针对梅毒螺旋体的全身炎症反应与其他病原体之间潜在的免疫学相互作用，以及这种相互作用如何影响局部的骨骼微环境，使骨骼生物标记物(如PD)能够以经验上的确定性用于重建IP。克雷斯波博士和他的同事致力于与当地和国家教育组织合作，就梅毒等性传播感染(STI)的健康和社会后果举办多次公共和K-12讲座；最终，强调通过生物考古学对过去人群中疾病的骨骼分析与现代生物医学分析(通过骨免疫学)相结合，如何改变目前对人类健康的理解。克雷斯波博士及其同事将尝试回答以下研究问题：(1)暴露在梅毒螺旋体下的人类免疫细胞是否会诱导全身炎症转移，从而影响宿主对梅毒螺旋体的免疫反应；(2)暴露在牙龈假单胞菌下的免疫细胞是否会诱导改变，从而影响宿主对梅毒螺旋体的免疫反应？(3)这种潜在的转移是否会对局部骨微环境产生下游影响，从而影响骨细胞的分化和活动？(4)最后，体外观察到的潜在炎症转移和生理变化是否与已证实感染梅毒螺旋体的骨骼中的PD有关？这些问题将使用来自健康捐赠者的外周血单核细胞(PBMC)来回答，将细胞群体分成两组：a)整个PBMC，以探索当细胞交替暴露于梅毒螺旋体和牙龈假单胞菌的抗原和裂解物时炎症转变的证据；以及b)分离的CD14+单核细胞，其分化为骨细胞，来自同一捐赠者，以评估潜在的转变可能如何影响骨细胞的分化和活性。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.