In order to accomplish our goals as defined above, we have developed and initiated a clinical protocol with the following primary objectives: 1. Clinical evaluation of oral manifestations in patients with immune dysfunction. 2. Characterization of oral immune response in patients with monogenic immune defects. 3. Characterization of the oral microbiome in patients with monogenic immune defects. ORAL MICROBIOME STUDIES Oral micobiome studies will characterize the bacterial colonization in the oral cavity in patients with monogenic defects. Microbial communities at mucosal surfaces are incredibly complex and their composition is affected by alterations of the immune system 34, 35. Until recently microbiome studies utilized culture based methodologies to identify and characterize bacterial colonization. With the recognition that as much as 60% of the human-associated microbiome is uncultivable and the evolution of sequencing methodologies (such as such as 454 pyrosequencing) we can know more accurately characterize the diversity of microbial colonization in the oral cavity at states of health and disruption of immune responses. Our clinical protocol has included sampling of the oral microbiome according to Human Microbiome Protocol (HMP) procedures. We have formed a collaborative team with NIH intramural and extramural Human Microbiome investigators to perform deep sequencing of 16S rRNA amplicon libraries and associated computational analysis on oral microbiome samples. STUDIES OF ORAL IMMUNE MECHANISMS The oral cavity is a unique environment for studying mucosal host defenses. Due to its accessibility we can non-invasively sample not only the bacteria on the tooth surface associated with health and disease but also the gingival crevicular fluid (an exudate from the periodontal pocket that contains locally produced immune mediators). Additionally, with minimally invasive procedures we can remove oral/gingival tissues to study the cellular composition, expression and production of immune mediators as well as engagement of signaling pathways that mediate health and disease in the oral cavity.
| Abusleme, Loreto; Diaz, Patricia I; Freeman, Alexandra F et al. (2018) Human defects in STAT3 promote oral mucosal fungal and bacterial dysbiosis. JCI Insight 3: |
| Abusleme, L; Moutsopoulos, N M (2017) IL-17: overview and role in oral immunity and microbiome. Oral Dis 23:854-865 |
| Moutsopoulos, Niki M; Zerbe, Christa S; Wild, Teresa et al. (2017) Interleukin-12 and Interleukin-23 Blockade in Leukocyte Adhesion Deficiency Type 1. N Engl J Med 376:1141-1146 |
| Shah, Nirali N; Freeman, Alexandra F; Su, Helen et al. (2017) Haploidentical Related Donor Hematopoietic Stem Cell Transplantation for Dedicator-of-Cytokinesis 8 Deficiency Using Post-Transplantation Cyclophosphamide. Biol Blood Marrow Transplant 23:980-990 |
| Dutzan, Nicolas; Konkel, Joanne E; Greenwell-Wild, Teresa et al. (2016) Characterization of the human immune cell network at the gingival barrier. Mucosal Immunol 9:1163-1172 |
| Hajishengallis, George; Moutsopoulos, Niki M (2016) Role of bacteria in leukocyte adhesion deficiency-associated periodontitis. Microb Pathog 94:21-6 |
| Falcone, E Liana; Abusleme, Loreto; Swamydas, Muthulekha et al. (2016) Colitis susceptibility in p47(phox-/-) mice is mediated by the microbiome. Microbiome 4:13 |
| Cuellar-Rodriguez, Jennifer; Freeman, Alexandra F; Grossman, Jennifer et al. (2015) Matched related and unrelated donor hematopoietic stem cell transplantation for DOCK8 deficiency. Biol Blood Marrow Transplant 21:1037-45 |
| Moutsopoulos, N M; Lionakis, M S; Hajishengallis, G (2015) Inborn errors in immunity: unique natural models to dissect oral immunity. J Dent Res 94:753-8 |
| Moutsopoulos, Niki M; Chalmers, Natalia I; Barb, Jennifer J et al. (2015) Subgingival microbial communities in Leukocyte Adhesion Deficiency and their relationship with local immunopathology. PLoS Pathog 11:e1004698 |
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