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


Leukocyte adhesion deficiency (LAD) is a primary immunodeficiency resulting from gene mutations in the CD18 subunit of β2 integrins that lead to defective neutrophil adhesion and transmigration into tissues. Affected patients suffer from recurrent life threatening infections and from a severe form of the oral disease periodontitis. The setting of this rare monogenic immune disorder provides a unique opportunity to explore consequences of defective neutrophil tissue transmigration on immunity and microbial colonization in barrier sites such as the oral mucosa. Furthermore, characterization of the oral- subgingival microbiome in LAD expands our understanding of LAD periodontitis, an aggressive disease which is recalcitrant to treatment and often leads to loss of the entire dentition in adolescence. Our current studies in a cohort of LAD patients show that the subgingival microbiome in LAD- periodontitis is unique in its composition and differs from that of health and aggressive periodontitis. Notably our studies reveal that the subgingival communities of LAD can serve as initial triggers for local immunopathology through translocation of bacterial products into tissues and stimulation of local IL-23-related destructive inflammatory responses.


Vyšlo v časopise: Subgingival Microbial Communities in Leukocyte Adhesion Deficiency and Their Relationship with Local Immunopathology. PLoS Pathog 11(3): e32767. doi:10.1371/journal.ppat.1004698
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004698

Souhrn

Leukocyte adhesion deficiency (LAD) is a primary immunodeficiency resulting from gene mutations in the CD18 subunit of β2 integrins that lead to defective neutrophil adhesion and transmigration into tissues. Affected patients suffer from recurrent life threatening infections and from a severe form of the oral disease periodontitis. The setting of this rare monogenic immune disorder provides a unique opportunity to explore consequences of defective neutrophil tissue transmigration on immunity and microbial colonization in barrier sites such as the oral mucosa. Furthermore, characterization of the oral- subgingival microbiome in LAD expands our understanding of LAD periodontitis, an aggressive disease which is recalcitrant to treatment and often leads to loss of the entire dentition in adolescence. Our current studies in a cohort of LAD patients show that the subgingival microbiome in LAD- periodontitis is unique in its composition and differs from that of health and aggressive periodontitis. Notably our studies reveal that the subgingival communities of LAD can serve as initial triggers for local immunopathology through translocation of bacterial products into tissues and stimulation of local IL-23-related destructive inflammatory responses.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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