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  1. Article ; Online: Neutrophils in the periodontium: Interactions with pathogens and roles in tissue homeostasis and inflammation

    Uriarte, Silvia M. / Hajishengallis, George

    Immunological Reviews 2023 Mar., v. 314, no. 1, p. 93-110

    2023  , Page(s) 93–110

    Abstract: Neutrophils are of key importance in periodontal health and disease. In their absence or when they are functionally defective, as occurs in certain congenital disorders, affected individuals develop severe forms of periodontitis in early age. These ... ...

    Abstract Neutrophils are of key importance in periodontal health and disease. In their absence or when they are functionally defective, as occurs in certain congenital disorders, affected individuals develop severe forms of periodontitis in early age. These observations imply that the presence of immune‐competent neutrophils is essential to homeostasis. However, the presence of supernumerary or hyper‐responsive neutrophils, either because of systemic priming or innate immune training, leads to imbalanced host–microbe interactions in the periodontium that culminate in dysbiosis and inflammatory tissue breakdown. These disease‐provoking imbalanced interactions are further exacerbated by periodontal pathogens capable of subverting neutrophil responses to their microbial community's benefit and the host's detriment. This review attempts a synthesis of these findings for an integrated view of the neutrophils' ambivalent role in periodontal disease and, moreover, discusses how some of these concepts underpin the development of novel therapeutic approaches to treat periodontal disease.
    Keywords dysbiosis ; homeostasis ; inflammation ; microbial communities ; mouth ; neutrophils ; periodontitis ; therapeutics
    Language English
    Dates of publication 2023-03
    Size p. 93-110
    Publishing place John Wiley & Sons, Inc
    Document type Article ; Online
    Note REVIEW
    ZDB-ID 391796-4
    ISSN 1600-065X ; 0105-2896
    ISSN (online) 1600-065X
    ISSN 0105-2896
    DOI 10.1111/imr.13152
    Database NAL-Catalogue (AGRICOLA)

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  2. Article ; Online: Neutrophils in the periodontium: Interactions with pathogens and roles in tissue homeostasis and inflammation.

    Uriarte, Silvia M / Hajishengallis, George

    Immunological reviews

    2022  Volume 314, Issue 1, Page(s) 93–110

    Abstract: Neutrophils are of key importance in periodontal health and disease. In their absence or when they are functionally defective, as occurs in certain congenital disorders, affected individuals develop severe forms of periodontitis in early age. These ... ...

    Abstract Neutrophils are of key importance in periodontal health and disease. In their absence or when they are functionally defective, as occurs in certain congenital disorders, affected individuals develop severe forms of periodontitis in early age. These observations imply that the presence of immune-competent neutrophils is essential to homeostasis. However, the presence of supernumerary or hyper-responsive neutrophils, either because of systemic priming or innate immune training, leads to imbalanced host-microbe interactions in the periodontium that culminate in dysbiosis and inflammatory tissue breakdown. These disease-provoking imbalanced interactions are further exacerbated by periodontal pathogens capable of subverting neutrophil responses to their microbial community's benefit and the host's detriment. This review attempts a synthesis of these findings for an integrated view of the neutrophils' ambivalent role in periodontal disease and, moreover, discusses how some of these concepts underpin the development of novel therapeutic approaches to treat periodontal disease.
    MeSH term(s) Humans ; Neutrophils ; Inflammation ; Periodontium ; Periodontitis ; Homeostasis
    Language English
    Publishing date 2022-10-22
    Publishing country England
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 391796-4
    ISSN 1600-065X ; 0105-2896
    ISSN (online) 1600-065X
    ISSN 0105-2896
    DOI 10.1111/imr.13152
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  3. Article ; Online: Periodontal Pathogens' strategies disarm neutrophils to promote dysregulated inflammation.

    Miralda, Irina / Uriarte, Silvia M

    Molecular oral microbiology

    2020  Volume 36, Issue 2, Page(s) 103–120

    Abstract: Periodontitis is an irreversible, chronic inflammatory disease where inflammophilic pathogenic microbial communities accumulate in the gingival crevice. Neutrophils are a major component of the innate host response against bacterial challenge, and under ... ...

    Abstract Periodontitis is an irreversible, chronic inflammatory disease where inflammophilic pathogenic microbial communities accumulate in the gingival crevice. Neutrophils are a major component of the innate host response against bacterial challenge, and under homeostatic conditions, their microbicidal functions typically protect the host against periodontitis. However, a number of periodontal pathogens developed survival strategies to evade neutrophil microbicidal functions while promoting inflammation, which provides a source of nutrients for bacterial growth. Research on periodontal pathogens has largely focused on a few established species: Tannerella forsythia, Treponema denticola, Fusobacterium nucleatum, Aggregatibacter actinomycetemcomitans, and Porphyromonas gingivalis. However, advances in culture-independent techniques have facilitated the identification of new bacterial species in periodontal lesions, such as the two Gram-positive anaerobes, Filifactor alocis and Peptoanaerobacter stomatis, whose characterization of pathogenic potential has not been fully described. Additionally, there is not a full understanding of the pathogenic mechanisms used against neutrophils by organisms that are abundant in periodontal lesions. This presents a substantial barrier to the development of new approaches to prevent or ameliorate the disease. In this review, we first summarize the neutrophil functions affected by the established periodontal pathogens listed above, denoting unknown areas that still merit a closer look. Then, we review the literature on neutrophil functions and the emerging periodontal pathogens, F. alocis and P. stomatis, comparing the effects of the emerging microbes to that of established pathogens, and speculate on the contribution of these putative pathogens to the progression of periodontal disease.
    MeSH term(s) Aggregatibacter actinomycetemcomitans ; Clostridiales ; Humans ; Inflammation ; Neutrophils ; Porphyromonas gingivalis ; Treponema denticola
    Language English
    Publishing date 2020-12-31
    Publishing country Denmark
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2537726-7
    ISSN 2041-1014 ; 2041-1006
    ISSN (online) 2041-1014
    ISSN 2041-1006
    DOI 10.1111/omi.12321
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The Hunger Games:

    Ozuna, Hazel / Uriarte, Silvia M / Demuth, Donald R

    Frontiers in immunology

    2021  Volume 12, Page(s) 707096

    Abstract: Aggregatibacter ... ...

    Abstract Aggregatibacter actinomycetemcomitans
    MeSH term(s) Aggregatibacter actinomycetemcomitans/metabolism ; Cell Survival/physiology ; Epinephrine/metabolism ; Humans ; Neutrophils/metabolism ; Pasteurellaceae Infections/metabolism ; Periodontitis/microbiology
    Chemical Substances Epinephrine (YKH834O4BH)
    Language English
    Publishing date 2021-08-12
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2021.707096
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Novel insights related to CF neutrophils.

    Uriarte, Silvia M

    Blood

    2014  Volume 124, Issue 7, Page(s) 985–986

    MeSH term(s) Cystic Fibrosis/metabolism ; Cystic Fibrosis Transmembrane Conductance Regulator/metabolism ; Female ; Humans ; Male ; Neutrophils/metabolism ; rab GTP-Binding Proteins/metabolism ; rab27 GTP-Binding Proteins
    Chemical Substances CFTR protein, human ; rab27 GTP-Binding Proteins ; Cystic Fibrosis Transmembrane Conductance Regulator (126880-72-6) ; RAB27A protein, human (EC 3.6.1.-.) ; rab GTP-Binding Proteins (EC 3.6.5.2)
    Language English
    Publishing date 2014-08-13
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood-2014-07-583831
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Aggregatibacter actinomycetemcomitans

    Ozuna, Hazel / Snider, Ian / Belibasakis, Georgios N / Oscarsson, Jan / Johansson, Anders / Uriarte, Silvia M

    Frontiers in oral health

    2022  Volume 3, Page(s) 981343

    Abstract: Periodontitis is a dysbiotic disease caused by the interplay between the microbial ecosystem present in the disease with the dysregulated host immune response. The disease-associated microbial community is formed by the presence of established oral ... ...

    Abstract Periodontitis is a dysbiotic disease caused by the interplay between the microbial ecosystem present in the disease with the dysregulated host immune response. The disease-associated microbial community is formed by the presence of established oral pathogens like
    Language English
    Publishing date 2022-08-15
    Publishing country Switzerland
    Document type Journal Article ; Review
    ISSN 2673-4842
    ISSN (online) 2673-4842
    DOI 10.3389/froh.2022.981343
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  7. Article ; Online: The emerging oral pathogen, Filifactor alocis, extends the functional lifespan of human neutrophils.

    Miralda, Irina / Vashishta, Aruna / Rogers, Max N / Lamont, Richard J / Uriarte, Silvia M

    Molecular microbiology

    2022  Volume 117, Issue 6, Page(s) 1340–1351

    Abstract: Periodontitis is a chronic inflammatory infectious disease that affects the integrity of tooth-supporting tissues and has adverse systemic consequences. Advances in sequencing technologies have uncovered organisms that are exclusively found in high ... ...

    Abstract Periodontitis is a chronic inflammatory infectious disease that affects the integrity of tooth-supporting tissues and has adverse systemic consequences. Advances in sequencing technologies have uncovered organisms that are exclusively found in high numbers in periodontal lesions, such as the gram-positive anaerobic rod, Filifactor alocis. F. alocis can manipulate neutrophil effector functions, which allows the organism to survive within these granulocytes. Several neutrophil functions have been tested in the context of F. alocis challenge, but the effect of the organism on neutrophil apoptosis is still unknown. RNA sequencing of human neutrophils challenged with F. alocis showed that apoptosis pathways were differentially regulated. Compared to media-cultured controls, F. alocis-challenged neutrophils maintain their nuclear morphology, do not stain for Annexin V or 7-AAD, and have decreased DNA fragmentation. Inhibition of apoptosis by F. alocis involved reduced caspase-3, -8, and - 9 activation and upregulation of important anti-apoptotic proteins. Prolonged lifespan was dependent on contact through TLR2/6, and F. alocis-challenged neutrophils retained their functional capacity to induce inflammation for longer timepoints. This is the first in-depth characterization of neutrophil apoptotic programs in response to an oral pathogen and provides key information on how bacteria manipulate immune cell mechanisms to maintain a dysregulated inflammatory response.
    MeSH term(s) Clostridiales ; Humans ; Longevity ; Neutrophils/microbiology ; Periodontitis/microbiology
    Language English
    Publishing date 2022-04-29
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 619315-8
    ISSN 1365-2958 ; 0950-382X
    ISSN (online) 1365-2958
    ISSN 0950-382X
    DOI 10.1111/mmi.14911
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  8. Article ; Online: Selenomonas sputigena Interactions with Gingival Epithelial Cells That Promote Inflammation.

    Hawkes, Colin G / Hinson, Annie N / Vashishta, Aruna / Read, Curtis B / Carlyon, Jason A / Lamont, Richard J / Uriarte, Silvia M / Miller, Daniel P

    Infection and immunity

    2023  Volume 91, Issue 2, Page(s) e0031922

    Abstract: Increased prevalence and abundance of Selenomonas sputigena have been associated with periodontitis, a chronic inflammatory disease of tooth-supporting tissues, for more than 50 years. Over the past decade, molecular surveys of periodontal disease using ... ...

    Abstract Increased prevalence and abundance of Selenomonas sputigena have been associated with periodontitis, a chronic inflammatory disease of tooth-supporting tissues, for more than 50 years. Over the past decade, molecular surveys of periodontal disease using 16S and shotgun metagenomic sequencing approaches have confirmed the disease association of classically recognized periodontal pathogens such as Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia while highlighting previously underappreciated organisms such as Filifactor alocis and S. sputigena. Despite abundant clinical association between
    MeSH term(s) Humans ; Inflammation ; Periodontitis/pathology ; Porphyromonas gingivalis/metabolism ; Periodontal Diseases ; Cytokines/metabolism ; Epithelial Cells/metabolism
    Chemical Substances Cytokines
    Language English
    Publishing date 2023-01-17
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 218698-6
    ISSN 1098-5522 ; 0019-9567
    ISSN (online) 1098-5522
    ISSN 0019-9567
    DOI 10.1128/iai.00319-22
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Neutrophil Interaction with Emerging Oral Pathogens: A Novel View of the Disease Paradigm.

    Miralda, Irina / Vashishta, Aruna / Uriarte, Silvia M

    Advances in experimental medicine and biology

    2019  Volume 1197, Page(s) 165–178

    Abstract: Periodontitis is a multifactorial chronic inflammatory infectious disease that compromises the integrity of tooth-supporting tissues. The disease progression depends on the disruption of host-microbe homeostasis in the periodontal tissue. This disruption ...

    Abstract Periodontitis is a multifactorial chronic inflammatory infectious disease that compromises the integrity of tooth-supporting tissues. The disease progression depends on the disruption of host-microbe homeostasis in the periodontal tissue. This disruption is marked by a shift in the composition of the polymicrobial oral community from a symbiotic to a dysbiotic, more complex community that is capable of evading killing while promoting inflammation. Neutrophils are the main phagocytic cell in the periodontal pocket, and the outcome of the interaction with the oral microbiota is an important determinant of oral health. Novel culture-independent techniques have facilitated the identification of new bacterial species at periodontal lesions and induced a reappraisal of the microbial etiology of periodontitis. In this chapter, we discuss how neutrophils interact with two emerging oral pathogens, Filifactor alocis and Peptoanaerobacter stomatis, and the different strategies deploy by these organisms to modulate neutrophil effector functions, with the goal to outline a new paradigm in our knowledge about neutrophil responses to putative periodontal pathogens and their contribution to disease progression.
    MeSH term(s) Clostridiales/immunology ; Dysbiosis ; Humans ; Microbiota/immunology ; Neutrophils/immunology ; Neutrophils/microbiology ; Periodontitis/immunology ; Periodontitis/microbiology ; Periodontium/microbiology
    Language English
    Publishing date 2019-11-15
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2214-8019 ; 0065-2598
    ISSN (online) 2214-8019
    ISSN 0065-2598
    DOI 10.1007/978-3-030-28524-1_12
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  10. Article: Human Neutrophil Granule Exocytosis in Response to

    Miralda, Irina / Klaes, Christopher K / Graham, James E / Uriarte, Silvia M

    Pathogens (Basel, Switzerland)

    2020  Volume 9, Issue 2

    Abstract: Mycobacterium ... ...

    Abstract Mycobacterium smegmatis
    Language English
    Publishing date 2020-02-15
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2695572-6
    ISSN 2076-0817
    ISSN 2076-0817
    DOI 10.3390/pathogens9020123
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