Bacterial Amyloids: The Link between Bacterial Infections and Autoimmunity

Nicastro, Lauren K.; Tükel, Çaǧla

doi:10.1016/j.tim.2019.07.002

Cited by 43 publications

(36 citation statements)

References 79 publications

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“…Nevertheless, extracellular DNA is known to facilitate the formation of functional amyloids in Staphylococcus biofilms (192), and PSMs are known to bind directly to human formyl peptide receptor 2 (FPR2) (193). Together, these studies strongly suggests a link between chronic bacterial infections, biofilms, and autoimmune diseases (13,194) (Figure 4). By therapeutically targeting curli amyloid fibers (195), disruption could potentially eradicate bacterial biofilms and secondary autoimmunity.…”

Section: Immunomodulatory Aspects Of Amyloids and Similarity To Ampsmentioning

confidence: 99%

“…Besides curli producing enteric bacteria, many important human pathogens such as Borrelia burgdorferi ( 184 ), Mycobacterium tuberculosis ( 185 ) , Pseudomonas aeruginosa ( 186 , 187 ), and Staphylococcus aureus ( 188 ) also produce amyloids. Individuals infected with these pathogens develop some form of autoimmune sequelae such as inflammatory arthritis ( 13 ). Phenol soluble modulins (PSMs) from Staphylococcus biofilms ( 189 – 191 ) and Fap amyloids from Pseudomonas biofilms ( 186 ) have been studied concisely, but at present, the mechanisms of DNA binding by other functional amyloids remain unclear, and it remains to be seen whether this has consequences for immune signaling and inflammation.…”

Section: Immunomodulatory Aspects Of Amyloids and Similarity To Ampsmentioning

confidence: 99%

“…Surprisingly, many amyloids possess hidden antimicrobial activity in addition to their known cytotoxic properties, suggesting a potential endogenous role in host defense ( 7 , 8 ). AMPs and bacterial amyloids have also been implicated in the pathogenesis of autoimmune diseases like lupus and psoriasis ( 5 , 9 – 13 ), parallel to the proinflammatory role of amyloids in neurodegeneration ( 14 ). Disentangling the molecular basis for the homeostatic and pathologic functions of both amyloids and AMPs has proven challenging ( 15 ).…”

Section: Introductionmentioning

confidence: 99%

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Functional Reciprocity of Amyloids and Antimicrobial Peptides: Rethinking the Role of Supramolecular Assembly in Host Defense, Immune Activation, and Inflammation

et al. 2020

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Section: Immunomodulatory Aspects Of Amyloids and Similarity To Ampsmentioning

confidence: 99%

Section: Immunomodulatory Aspects Of Amyloids and Similarity To Ampsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Functional Reciprocity of Amyloids and Antimicrobial Peptides: Rethinking the Role of Supramolecular Assembly in Host Defense, Immune Activation, and Inflammation

et al. 2020

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“…These bacterial amyloids are adaptive, help the organisms stick together, and protect bacterial communities by resisting destruction by viruses and other agents. Bacterial amyloids have been linked to infections as well to autoimmunity [9]. In 2015, Friedland proposed that bacterial amyloid may cross-seed the aggregation of neuronal proteins such as Aβ, alpha synuclein (AS), tau and others to initiate a prion-like propagation [10].…”

Section: Functional Bacterial Amyloid Proteins (Fuba) May Cross-seed mentioning

confidence: 99%

What Are the Molecular Mechanisms by Which Functional Bacterial Amyloids Influence Amyloid Beta Deposition and Neuroinflammation in Neurodegenerative Disorders?

Friedland

McMillan

Kurlawala

2020

IJMS

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Despite the enormous literature documenting the importance of amyloid beta (Ab) protein in Alzheimer's disease, we do not know how Ab aggregation is initiated and why it has its unique distribution in the brain. In vivo and in vitro evidence has been developed to suggest that functional microbial amyloid proteins produced in the gut may cross-seed Ab aggregation and prime the innate immune system to have an enhanced and pathogenic response to neuronal amyloids. In this commentary, we summarize the molecular mechanisms by which the microbiota may initiate and sustain the pathogenic processes of neurodegeneration in aging.

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“…Moreover, infections can release host nucleic acids in the extracellular compartment because of the different types of cell death that can occur during infection, either as a direct cytotoxicity of the pathogen or as a consequence of normal immune responses, notably pyroptosis (33) and the extrusion of neutrophil extracellular traps (NETs) (11, 34). The interplay between infections, biofilms and cell death continues to be the focus of much discussion in the field (35–38).…”

Section: Introductionmentioning

confidence: 99%

Triggers of Autoimmunity: The Role of Bacterial Infections in the Extracellular Exposure of Lupus Nuclear Autoantigens

2019

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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.

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Bacterial Amyloids: The Link between Bacterial Infections and Autoimmunity

Cited by 43 publications

References 79 publications

Functional Reciprocity of Amyloids and Antimicrobial Peptides: Rethinking the Role of Supramolecular Assembly in Host Defense, Immune Activation, and Inflammation

Functional Reciprocity of Amyloids and Antimicrobial Peptides: Rethinking the Role of Supramolecular Assembly in Host Defense, Immune Activation, and Inflammation

What Are the Molecular Mechanisms by Which Functional Bacterial Amyloids Influence Amyloid Beta Deposition and Neuroinflammation in Neurodegenerative Disorders?

Triggers of Autoimmunity: The Role of Bacterial Infections in the Extracellular Exposure of Lupus Nuclear Autoantigens

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