Human Barrier Immunity Section
Niki M. Moutsopoulos, D.D.S., Ph.D.
Chief, Laboratory of Host Immunity and Microbiome
Chief, Human Barrier Immunity Section
Contact: For contact information, search the NIH Enterprise Directory.
Provides direct clinical care to patients at NIH Clinical Center
Major Areas of Research
- Mucosal Immunology
- Human Immunology
- Host/microbe Interactions
- Oral mucosal Immunity/Periodontal Disease
Program Description
Dr. Moutsopoulos’ research is focused on oral-barrier immunity. The oral mucosa is a site of first encounters for the mammalian host. Food, airborne particles, and commensal microbiota are first encountered here as they enter the gastrointestinal and respiratory tracts. Yet, how the local immune system can tolerate innocuous antigens and commensals in health while conferring protection from pathogens is not well understood. Moreover, understanding how the balance between environment and host becomes dysregulated, leading to oral mucosal disease, is of great clinical importance.
Oral mucosal diseases include common oral-specific conditions, such as the prevalent inflammatory disease periodontitis, but can also often be a manifestation of systemic immune dysregulation in the context of immunodeficiency and/or autoimmunity. Therefore, understanding tissue-specific immunity at this barrier opens doors toward the understanding and therapeutic targeting of both local and widespread barrier disease manifestations.
Studies in the lab implement a bedside-to-bench and back approach. Research questions are initiated through patient-centric observations related to clinical problems and are taken to the bench to pursue studies of human tissue and systemic immunity, with the intent to capture signatures of human health and disease. Mechanistic insights into homeostatic and pathologic inflammatory pathways are gained through studies in animal models of disease and through vivo and ex vivo experimentation. Leveraging the strengths of the intramural program, her team has particularly focused on the study of patients with Mendelian diseases, which present with severe oral mucosal manifestations. Studies in patients with Mendelian disease have allowed us to care for patients with severe clinical phenotypes and have provided insights into human biology that can be relevant to common forms of human mucosal disease.
Biography
Education
D.D.S., Aristotle University of Thessaloniki, Greece
Ph.D., University of Maryland Baltimore/National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD
Dr. Moutsopoulos received a D.D.S. degree from the Aristotle University of Thessaloniki, Greece, completed her specialization in periodontology at the University of Maryland, and obtained a Ph.D. in immunology from the University of Maryland while working in the laboratory of Dr. Sharon Wahl at the NIH National Institute of Dental and Craniofacial Research. Following her Ph.D., she remained at NIH as a clinical fellow and then as an associate clinical investigator focusing on human immunology through the study of patients with monogenic immune defects under the mentorship of Dr. Steven Holland (LCID/NIAID).
As an independent investigator at NIH, Dr. Moutsopoulos has built a clinical and translational program studying human barrier immunity with a focus on oral mucosal immunology. Her scientific work and mentoring efforts have been recognized through multiple awards, including the International Association for Dental, Oral, and Craniofacial Research (IADR) Women in Science Award for Distinguished Female Mentor in 2019 and the IADR Distinguished Scientist Award for Craniofacial Biology Research in Oral Biology in 2023. She was elected to the Henry Kunkel Society in 2022 and the National Academy of Medicine in 2024.
Clinical Studies
- Oral Bacteria and Immune System Problems Involved in Gum Disease (Periodontitis)
- ClinicalTrials.gov ID NCT01568697
- Principal Investigator: Niki M. Moutsopoulos
- Keywords: Microbiome, Periodontitis, Oral Mucosal Immunity, Oral Infection, Natural History, Immune Disorder, Periodontal Disease, Gum Disease, Healthy Volunteer, HV, Mouth Diseases, Stomatognathic Diseases, Periodontal Diseases
Selected Publications
Kim TS, Ikeuchi T, Theofilou VI, Williams DW, Greenwell-Wild T, June A, Adade EE, Li L, Abusleme L, Dutzan N, Yuan Y, Brenchley L, Bouladoux N, Sakamachi Y, NIDCD/NIDCR Genomics and Computational Biology Core, Palmer RJ Jr, Iglesias-Bartolome R, Trinchieri G, Garantziotis S, Belkaid Y, Valm AM, Diaz PI, Holland SM, Moutsopoulos NM. Epithelial-derived interleukin-23 promotes oral mucosal immunopathology. Immunity. 2024;57(4):859-875.e11.
Silva LM, Doyle AD, Greenwell-Wild T, Dutzan N, Tran CL, Abusleme L, Juang LJ, Leung J, Chun EM, Lum AG, Agler CS, Zuazo CE, Sibree M, Jani P, Kram V, Martin D, Moss K, Lionakis MS, Castellino FJ, Kastrup CJ, Flick MJ, Divaris K, Bugge TH, Moutsopoulos NM. Fibrin is a critical regulator of neutrophil effector function at the oral mucosal barrier. Science. 2021;374(6575):eabl5450.
Williams DW, Greenwell-Wild T, Brenchley L, Dutzan N, Overmiller A, Sawaya AP, Webb S, Martin D, NIDCD/NIDCR Genomics and Computational Biology Core, Hajishengallis G, Divaris K, Morasso M, Haniffa M, Moutsopoulos NM. Human oral mucosa cell atlas reveals a stromal-neutrophil axis regulating tissue immunity. Cell. 2021;184(15):4090-4104.e15.
Break TJ, Oikonomou V, Dutzan N, Desai JV, Swidergall M, Freiwald T, Chauss D, Harrison OJ, Alejo J, Williams DW, Pittaluga S, Lee CR, Bouladoux N, Swamydas M, Hoffman KW, Greenwell-Wild T, Bruno VM, Rosen LB, Lwin W, Renteria A, Pontejo SM, Shannon JP, Myles IA, Olbrich P, Ferré EMN, Schmitt M, Martin D; Genomics and Computational Biology Core; Barber DL, Solis NV, Notarangelo LD, Serreze DV, Matsumoto M, Hickman HD, Murphy PM, Anderson MS, Lim JK, Holland SM, Filler SG, Afzali B, Belkaid Y, Moutsopoulos NM, Lionakis MS. Aberrant type 1 immunity drives susceptibility to mucosal fungal infections. Science. 2021 Jan 15;371(6526):eaay5731.
Dutzan N, Kajikawa T, Abusleme L, Greenwell-Wild T, Zuazo CE, Ikeuchi T, Brenchley L, Abe T, Hurabielle C, Martin D, Morell RJ, Freeman AF, Lazarevic V, Trinchieri G, Diaz PI, Holland SM, Belkaid Y, Hajishengallis G, Moutsopoulos NM. A dysbiotic microbiome triggers TH17 cells to mediate oral mucosal immunopathology in mice and humans. Sci Transl Med. 2018 Oct 17;10(463):eaat0797.
Moutsopoulos NM, Zerbe CS, Wild T, Dutzan N, Brenchley L, DiPasquale G, Uzel G, Axelrod KC, Lisco A, Notarangelo LD, Hajishengallis G, Notarangelo LD, Holland SM. Interleukin-12 and Interleukin-23 Blockade in Leukocyte Adhesion Deficiency Type 1. N Engl J Med. 2017;376(12):1141-1146.