In a susceptible host, persistence of periodontal pathogens such as P. gingivalis results in aberrant and prolonged inflammation and subsequent tissue damage of the tooth supporting structures, namely periodontitis. Tissue pathology is largely the consequence of chronic release of factors by activated cells of the immune system. Among the immune cells responding to challenge by bacteria, including P. gingivalis, are antigen presenting cells (APC) of myeloid origin such as monocytes, macrophages and dendritic cells, strategically poised along portals of entry or recruited to sites of infection. After recognition of pathogen associated molecular patterns (PAMPs) via toll like receptors (TLR), innate immune cells initiate responses aiming to contain and/or clear the inciting agent. As coordinators, APC also orchestrate the transition to the adaptive arm of the immune response, including the generation of effector T cell responses. Effector T cells were previously considered to differentiate into either a Th1 or Th2 phenotype, but with the recent recognition of effector T cell plasticity and the Th17 lineage, there has been an emphasis on characterizing the contributing cells involved in chronic mucosal lesions. IL-17 secreting Th17 cells play a protective role in antimicrobial immunity but have also been linked to inflammatory and autoimmune pathologies. Persistence of the Th17 population has been shown to support chronicity of inflammation and to directly mediate tissue destruction, via activation of resident matrix cells such as fibroblasts and osteoclasts, unlike Th1/Th2 cells which can inhibit osteoclast differentiation. Immune-mediated osseous destruction is the hallmark of periodontal disease and, hence, delineating a role for Th1/Th2/Th17 lineages in periodontitis is ongoing, in an effort to further the understanding of disease pathologies and ultimately uncover possible targets to disrupt pathogenesis. To this end, we aimed to study the Th lineage representation within the pathologic lesions of periodontitis and to investigate possible mechanisms by which strains of the periodontal pathogen P. gingivalis which are considered more or less virulent may orchestrate T cell lineage commitment relevant to oral mucosal immunopathology. To delineate immune cell-dependent mechanisms whereby bacterial challenge drives persistent destructive inflammation, we studied involved tissues ex vivo from patients with severe periodontitis. Diseased lesions were populated by abundant Th17 cells, a cell type linked to infection, chronic inflammation/autoimmunity and tissue pathology. To dissect mechanisms by which Th17 cells may be induced in periodontitis we studied the interaction of the periodontal pathogen P. gingivalis with innate immune cells and their potential to differentially drive Th cell responses. We found that P. gingivalis, particularly its virulent strain W83, stimulated myeloid antigen presenting cells to produce cytokines linked to Th17 polarization, such as IL-1 and IL-6, and not Th1 cytokines, favoring a Th17 response. Promotion of Th17 lineage responses was also aided by P. gingivalis proteases, which appeared to differentially degrade pivotal cytokines. In this regard, IL-12 was largely degraded by P. gingivalis, whereas IL-1 was more resistant to proteolysis. Our data unveil multiple pathways by which P. gingivalis may orchestrate chronic inflammation, providing insights into interventional strategies.

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National Institute of Dental & Craniofacial Research
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Moutsopoulos, Niki M; Konkel, Joanne E (2018) Tissue-Specific Immunity at the Oral Mucosal Barrier. Trends Immunol 39:276-287
Konkel, J E; Moutsopoulos, N M (2018) Unique Tailoring of Th17 at the Gingival Oral Mucosal Barrier. J Dent Res 97:128-131
Abusleme, Loreto; Hong, Bo-Young; Hoare, Anilei et al. (2017) Oral Microbiome Characterization in Murine Models. Bio Protoc 7:
Dutzan, Nicolas; Abusleme, Loreto; Bridgeman, Hayley et al. (2017) On-going Mechanical Damage from Mastication Drives Homeostatic Th17 Cell Responses at the Oral Barrier. Immunity 46:133-147
Abusleme, L; Moutsopoulos, N M (2017) IL-17: overview and role in oral immunity and microbiome. Oral Dis 23:854-865
Konig, Maximilian F; Abusleme, Loreto; Reinholdt, Jesper et al. (2016) Aggregatibacter actinomycetemcomitans-induced hypercitrullination links periodontal infection to autoimmunity in rheumatoid arthritis. Sci Transl Med 8:369ra176
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
Dutzan, Nicolas; Abusleme, Loreto; Konkel, Joanne E et al. (2016) Isolation, Characterization and Functional Examination of the Gingival Immune Cell Network. J Vis Exp :53736
Hajishengallis, George; Moutsopoulos, Niki M (2014) Etiology of leukocyte adhesion deficiency-associated periodontitis revisited: not a raging infection but a raging inflammatory response. Expert Rev Clin Immunol 10:973-5
Moutsopoulos, Niki M; Konkel, Joanne; Sarmadi, Mojgan et al. (2014) Defective neutrophil recruitment in leukocyte adhesion deficiency type I disease causes local IL-17-driven inflammatory bone loss. Sci Transl Med 6:229ra40

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