Triggers of Autoimmunity: The Role of Bacterial Infections in the Extracellular Exposure of Lupus Nuclear Autoantigens
Infections are considered important environmental triggers of autoimmunity and can contribute to autoimmune disease onset and severity. Nucleic acids and the complexes that they form with proteins—including chromatin and ribonucleoproteins—are the main autoantigens in the autoimmune disease systemic...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.02608/full |
| _version_ | 1818450063744040960 |
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| author | Connie C. Qiu Roberto Caricchio Stefania Gallucci |
| author_facet | Connie C. Qiu Roberto Caricchio Stefania Gallucci |
| author_sort | Connie C. Qiu |
| collection | DOAJ |
| description | Infections are considered important environmental triggers of autoimmunity and can contribute to autoimmune disease onset and severity. Nucleic acids and the complexes that they form with proteins—including chromatin and ribonucleoproteins—are the main autoantigens in the autoimmune disease systemic lupus erythematosus (SLE). How these nuclear molecules become available to the immune system for recognition, presentation, and targeting is an area of research where complexities remain to be disentangled. In this review, we discuss how bacterial infections participate in the exposure of nuclear autoantigens to the immune system in SLE. Infections can instigate pro-inflammatory cell death programs including pyroptosis and NETosis, induce extracellular release of host nuclear autoantigens, and promote their recognition in an immunogenic context by activating the innate and adaptive immune systems. Moreover, bacterial infections can release bacterial DNA associated with other bacterial molecules, complexes that can elicit autoimmunity by acting as innate stimuli of pattern recognition receptors and activating autoreactive B cells through molecular mimicry. Recent studies have highlighted SLE disease activity-associated alterations of the gut commensals and the expansion of pathobionts that can contribute to chronic exposure to extracellular nuclear autoantigens. A novel field in the study of autoimmunity is the contribution of bacterial biofilms to the pathogenesis of autoimmunity. Biofilms are multicellular communities of bacteria that promote colonization during chronic infections. We review the very recent literature highlighting a role for bacterial biofilms, and their major components, amyloid/DNA complexes, in the generation of anti-nuclear autoantibodies and their ability to stimulate the autoreactive immune response. The best studied bacterial amyloid is curli, produced by enteric bacteria that commonly cause infections in SLE patients, including Escherichia coli and Salmonella spps. Evidence suggests that curli/DNA complexes can trigger autoimmunity by acting as danger signals, molecular mimickers, and microbial chaperones of nucleic acids. |
| first_indexed | 2024-12-14T20:45:21Z |
| format | Article |
| id | doaj.art-070e3a4cc94346ae8cc2c8ce134e82bc |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T20:45:21Z |
| publishDate | 2019-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-070e3a4cc94346ae8cc2c8ce134e82bc2022-12-21T22:48:03ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-11-011010.3389/fimmu.2019.02608465543Triggers of Autoimmunity: The Role of Bacterial Infections in the Extracellular Exposure of Lupus Nuclear AutoantigensConnie C. Qiu0Roberto Caricchio1Stefania Gallucci2Laboratory of Dendritic Cell Biology, Department of Microbiology and Immunology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, United StatesDivision of Rheumatology, Department of Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, United StatesLaboratory of Dendritic Cell Biology, Department of Microbiology and Immunology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, United StatesInfections are considered important environmental triggers of autoimmunity and can contribute to autoimmune disease onset and severity. Nucleic acids and the complexes that they form with proteins—including chromatin and ribonucleoproteins—are the main autoantigens in the autoimmune disease systemic lupus erythematosus (SLE). How these nuclear molecules become available to the immune system for recognition, presentation, and targeting is an area of research where complexities remain to be disentangled. In this review, we discuss how bacterial infections participate in the exposure of nuclear autoantigens to the immune system in SLE. Infections can instigate pro-inflammatory cell death programs including pyroptosis and NETosis, induce extracellular release of host nuclear autoantigens, and promote their recognition in an immunogenic context by activating the innate and adaptive immune systems. Moreover, bacterial infections can release bacterial DNA associated with other bacterial molecules, complexes that can elicit autoimmunity by acting as innate stimuli of pattern recognition receptors and activating autoreactive B cells through molecular mimicry. Recent studies have highlighted SLE disease activity-associated alterations of the gut commensals and the expansion of pathobionts that can contribute to chronic exposure to extracellular nuclear autoantigens. A novel field in the study of autoimmunity is the contribution of bacterial biofilms to the pathogenesis of autoimmunity. Biofilms are multicellular communities of bacteria that promote colonization during chronic infections. We review the very recent literature highlighting a role for bacterial biofilms, and their major components, amyloid/DNA complexes, in the generation of anti-nuclear autoantibodies and their ability to stimulate the autoreactive immune response. The best studied bacterial amyloid is curli, produced by enteric bacteria that commonly cause infections in SLE patients, including Escherichia coli and Salmonella spps. Evidence suggests that curli/DNA complexes can trigger autoimmunity by acting as danger signals, molecular mimickers, and microbial chaperones of nucleic acids.https://www.frontiersin.org/article/10.3389/fimmu.2019.02608/fullautoantigensautoantibodiesextracellular DNAbacterial infectionslupus (SLE) |
| spellingShingle | Connie C. Qiu Roberto Caricchio Stefania Gallucci Triggers of Autoimmunity: The Role of Bacterial Infections in the Extracellular Exposure of Lupus Nuclear Autoantigens Frontiers in Immunology autoantigens autoantibodies extracellular DNA bacterial infections lupus (SLE) |
| title | Triggers of Autoimmunity: The Role of Bacterial Infections in the Extracellular Exposure of Lupus Nuclear Autoantigens |
| title_full | Triggers of Autoimmunity: The Role of Bacterial Infections in the Extracellular Exposure of Lupus Nuclear Autoantigens |
| title_fullStr | Triggers of Autoimmunity: The Role of Bacterial Infections in the Extracellular Exposure of Lupus Nuclear Autoantigens |
| title_full_unstemmed | Triggers of Autoimmunity: The Role of Bacterial Infections in the Extracellular Exposure of Lupus Nuclear Autoantigens |
| title_short | Triggers of Autoimmunity: The Role of Bacterial Infections in the Extracellular Exposure of Lupus Nuclear Autoantigens |
| title_sort | triggers of autoimmunity the role of bacterial infections in the extracellular exposure of lupus nuclear autoantigens |
| topic | autoantigens autoantibodies extracellular DNA bacterial infections lupus (SLE) |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.02608/full |
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