Subgingival Microbial Communities in Leukocyte Adhesion Deficiency and Their Relationship with Local Immunopathology

PLoS Pathogens

Daniel H. Fine¹  Jennifer J. Barb¹  Natalia I. Chalmers²  Peter J. Munson³  Steven M. Holland⁴  Niki M. Moutsopoulos⁵  Nicolas Dutzan⁵  Loreto Abusleme⁵  Teresa Greenwell-Wild⁵  Gulbu Uzel⁶  Bruce J. Paster⁷ 

[1] Center for Information Technology, National Institutes of Health, Bethesda, Maryland, United States of America;Clinical Research Core, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United States of America;Harvard School of Dental Medicine, Boston, Massachusetts, United States of America;National Institute of Allergy and Infectious Diseases, Laboratory of Clinical Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America;Oral Immunity and Inflammation Unit, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United States of America;Rutgers School of Dental Medicine, Rutgers University, Newark, New Jersey, United States of America;The Forsyth Institute, Cambridge, Massachusetts, United States of America

关键词: Periodontitis;    Microbiome;    Inflammation;    Bacteria;    Neutrophils;    Immune deficiency;    Macrophages;    Microarrays;   

DOI  :  10.1371/journal.ppat.1004698

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Leukocyte Adhesion Deficiency I (LAD-I) is a primary immunodeficiency caused by single gene mutations in the CD18 subunit of β2 integrins which result in defective transmigration of neutrophils into the tissues. Affected patients suffer from recurrent life threatening infections and severe oral disease (periodontitis). Microbial communities in the local environment (subgingival plaque) are thought to be the triggers for inflammatory periodontitis, yet little is known regarding the microbial communities associated with LAD-I periodontitis. Here we present the first comprehensive characterization of the subgingival communities in LAD-I, using a 16S rRNA gene-based microarray, and investigate the relationship of this tooth adherent microbiome to the local immunopathology of periodontitis. We show that the LAD subgingival microbiome is distinct from that of health and Localized Aggressive Periodontitits. Select periodontitis-associated species in the LAD microbiome included Parvimonas micra, Porphyromonas endodontalis, Eubacterium brachy and Treponema species. Pseudomonas aeruginosa, a bacterium not typically found in subgingival plaque is detected in LAD-I. We suggest that microbial products from LAD-associated communities may have a role in stimulating the local inflammatory response. We demonstrate that bacterial LPS translocates into the lesions of LAD-periodontitis potentially triggering immunopathology. We also show in in vitro assays with human macrophages and in vivo in animal models that microbial products from LAD-associated subgingival plaque trigger IL-23-related immune responses, which have been shown to dominate in patient lesions. In conclusion, our current study characterizes the subgingival microbial communities in LAD-periodontitis and supports their role as triggers of disease pathogenesis.

【 授权许可】

CC BY