Crosstalk of Microorganisms and Immune Responses in Autoimmune Neuroinflammation: A Focus on Regulatory T Cells

Regulatory T cells (Tregs) are the major determinant of peripheral immune tolerance. Many Treg subsets have been described, however thymus-derived and peripherally induced Tregs remain the most important subpopulations. In multiple sclerosis, a prototypical autoimmune disorder of the central nervous...

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Published inFrontiers in immunology Vol. 12; p. 747143
Main Authors Schroeter, Christina B, Huntemann, Niklas, Bock, Stefanie, Nelke, Christopher, Kremer, David, Pfeffer, Klaus, Meuth, Sven G, Ruck, Tobias
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 07.10.2021
Subjects
Animals
Autoimmune Diseases - immunology
Autoimmune Diseases - microbiology
autoimmunity
Humans
Immunology
microorganism
neuroinflammation
Neuroinflammatory Diseases - immunology
Neuroinflammatory Diseases - microbiology
pathogens
Persistent Infection - immunology
regulatory T cells
T cells
T-Lymphocytes, Regulatory - immunology
regulatory T cells
immunometabolomics
autoimmunity
pathogens
neuroinflammation
microorganism
T cells
microbiome
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Abstract Regulatory T cells (Tregs) are the major determinant of peripheral immune tolerance. Many Treg subsets have been described, however thymus-derived and peripherally induced Tregs remain the most important subpopulations. In multiple sclerosis, a prototypical autoimmune disorder of the central nervous system, Treg dysfunction is a pathogenic hallmark. In contrast, induction of Treg proliferation and enhancement of their function are central immune evasion mechanisms of infectious pathogens. In accordance, Treg expansion is compartmentalized to tissues with high viral replication and prolonged in chronic infections. In friend retrovirus infection, Treg expansion is mainly based on excessive interleukin-2 production by infected effector T cells. Moreover, pathogens seem also to enhance Treg functions as shown in human immunodeficiency virus infection, where Tregs express higher levels of effector molecules such as cytotoxic T-lymphocyte-associated protein 4, CD39 and cAMP and show increased suppressive capacity. Thus, insights into the molecular mechanisms by which intracellular pathogens alter Treg functions might aid to find new therapeutic approaches to target central nervous system autoimmunity. In this review, we summarize the current knowledge of the role of pathogens for Treg function in the context of autoimmune neuroinflammation. We discuss the mechanistic implications for future therapies and provide an outlook for new research directions.
AbstractList Regulatory T cells (Tregs) are the major determinant of peripheral immune tolerance. Many Treg subsets have been described, however thymus-derived and peripherally induced Tregs remain the most important subpopulations. In multiple sclerosis, a prototypical autoimmune disorder of the central nervous system, Treg dysfunction is a pathogenic hallmark. In contrast, induction of Treg proliferation and enhancement of their function are central immune evasion mechanisms of infectious pathogens. In accordance, Treg expansion is compartmentalized to tissues with high viral replication and prolonged in chronic infections. In friend retrovirus infection, Treg expansion is mainly based on excessive interleukin-2 production by infected effector T cells. Moreover, pathogens seem also to enhance Treg functions as shown in human immunodeficiency virus infection, where Tregs express higher levels of effector molecules such as cytotoxic T-lymphocyte-associated protein 4, CD39 and cAMP and show increased suppressive capacity. Thus, insights into the molecular mechanisms by which intracellular pathogens alter Treg functions might aid to find new therapeutic approaches to target central nervous system autoimmunity. In this review, we summarize the current knowledge of the role of pathogens for Treg function in the context of autoimmune neuroinflammation. We discuss the mechanistic implications for future therapies and provide an outlook for new research directions.
Author Schroeter, Christina B
Huntemann, Niklas
Nelke, Christopher
Bock, Stefanie
Kremer, David
Ruck, Tobias
Pfeffer, Klaus
Meuth, Sven G
AuthorAffiliation 2 Department of Neurology With Institute of Translational Neurology, University of Münster , Münster , Germany
1 Department of Neurology, Medical Faculty, Heinrich Heine University Düsseldorf , Düsseldorf , Germany
3 Institute of Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University Düsseldorf , Düsseldorf , Germany
AuthorAffiliation_xml – name: 2 Department of Neurology With Institute of Translational Neurology, University of Münster , Münster , Germany
– name: 1 Department of Neurology, Medical Faculty, Heinrich Heine University Düsseldorf , Düsseldorf , Germany
– name: 3 Institute of Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University Düsseldorf , Düsseldorf , Germany
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  givenname: Niklas
  surname: Huntemann
  fullname: Huntemann, Niklas
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  surname: Bock
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  organization: Department of Neurology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
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  fullname: Kremer, David
  organization: Department of Neurology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
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  surname: Pfeffer
  fullname: Pfeffer, Klaus
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– sequence: 7
  givenname: Sven G
  surname: Meuth
  fullname: Meuth, Sven G
  organization: Department of Neurology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
– sequence: 8
  givenname: Tobias
  surname: Ruck
  fullname: Ruck, Tobias
  organization: Department of Neurology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
BackLink https://www.ncbi.nlm.nih.gov/pubmed/34691057$$D View this record in MEDLINE/PubMed
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Keywords regulatory T cells
immunometabolomics
autoimmunity
pathogens
neuroinflammation
microorganism
T cells
microbiome
Language English
License Copyright © 2021 Schroeter, Huntemann, Bock, Nelke, Kremer, Pfeffer, Meuth and Ruck.
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This article was submitted to Multiple Sclerosis and Neuroimmunology, a section of the journal Frontiers in Immunology
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Snippet Regulatory T cells (Tregs) are the major determinant of peripheral immune tolerance. Many Treg subsets have been described, however thymus-derived and...
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SubjectTerms Animals
Autoimmune Diseases - immunology
Autoimmune Diseases - microbiology
autoimmunity
Humans
Immunology
microorganism
neuroinflammation
Neuroinflammatory Diseases - immunology
Neuroinflammatory Diseases - microbiology
pathogens
Persistent Infection - immunology
regulatory T cells
T cells
T-Lymphocytes, Regulatory - immunology
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Title Crosstalk of Microorganisms and Immune Responses in Autoimmune Neuroinflammation: A Focus on Regulatory T Cells
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Volume 12
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