Subgingival microbial communities in Leukocyte Adhesion Deficiency and their relationship with local immunopathology.
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.
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.
Niki M
NM
Moutsopoulos
Clinical Research Core, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United States of America.
Natalia I
NI
Chalmers
Center for Information Technology, National Institutes of Health, Bethesda, Maryland, United States of America.
Jennifer J
JJ
Barb
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.
Loreto
L
Abusleme
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.
Teresa
T
Greenwell-Wild
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.
Nicolas
N
Dutzan
The Forsyth Institute, Cambridge, Massachusetts, United States of America; Harvard School of Dental Medicine, Boston, Massachusetts, United States of America.
Bruce J
BJ
Paster
Center for Information Technology, National Institutes of Health, Bethesda, Maryland, United States of America.
Peter J
PJ
Munson
Rutgers School of Dental Medicine, Rutgers University, Newark, New Jersey, United States of America.
Daniel H
DH
Fine
National Institute of Allergy and Infectious Diseases, Laboratory of Clinical Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Gulbu
G
Uzel
National Institute of Allergy and Infectious Diseases, Laboratory of Clinical Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Steven M
SM
Holland
D000818:Animals; D004269:DNA, Bacterial / Q000235:genetics / Q000276:immunology; D003773:Dental Plaque / Q000235:genetics; D006801:Humans; D053759:Interleukin-23 / Q000378:metabolism; D018370:Leukocyte-Adhesion Deficiency Syndrome / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D007962:Leukocytes / Q000276:immunology*; D051379:Mice; D064307:Microbiota / Q000276:immunology; D010518:Periodontitis / Q000382:microbiology*; D016966:Porphyromonas gingivalis; D012336:RNA, Ribosomal, 16S / Q000235:genetics
D004269:DNA, Bacterial; D053759:Interleukin-23; D012336:RNA, Ribosomal, 16S