Underwhelming or Misunderstood? Genetic Variability of Pattern Recognition Receptors in Immune Responses and Resistance to Mycobacterium tuberculosis
Human genetic control is thought to affect a considerable part of the outcome of infection with Mycobacterium tuberculosis (Mtb). Most of us deal with the pathogen by containment (associated with clinical “latency”) or sterilization, but tragically millions each year do not. After decades of studies...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.714808/full |
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| author | Jean-Yves Dubé Jean-Yves Dubé Jean-Yves Dubé Vinicius M. Fava Vinicius M. Fava Erwin Schurr Erwin Schurr Erwin Schurr Erwin Schurr Erwin Schurr Marcel A. Behr Marcel A. Behr Marcel A. Behr Marcel A. Behr |
| author_facet | Jean-Yves Dubé Jean-Yves Dubé Jean-Yves Dubé Vinicius M. Fava Vinicius M. Fava Erwin Schurr Erwin Schurr Erwin Schurr Erwin Schurr Erwin Schurr Marcel A. Behr Marcel A. Behr Marcel A. Behr Marcel A. Behr |
| author_sort | Jean-Yves Dubé |
| collection | DOAJ |
| description | Human genetic control is thought to affect a considerable part of the outcome of infection with Mycobacterium tuberculosis (Mtb). Most of us deal with the pathogen by containment (associated with clinical “latency”) or sterilization, but tragically millions each year do not. After decades of studies on host genetic susceptibility to Mtb infection, genetic variation has been discovered to play a role in tuberculous immunoreactivity and tuberculosis (TB) disease. Genes encoding pattern recognition receptors (PRRs) enable a consistent, molecularly direct interaction between humans and Mtb which suggests the potential for co-evolution. In this review, we explore the roles ascribed to PRRs during Mtb infection and ask whether such a longstanding and intimate interface between our immune system and this pathogen plays a critical role in determining the outcome of Mtb infection. The scientific evidence to date suggests that PRR variation is clearly implicated in altered immunity to Mtb but has a more subtle role in limiting the pathogen and pathogenesis. In contrast to ‘effectors’ like IFN-γ, IL-12, Nitric Oxide and TNF that are critical for Mtb control, ‘sensors’ like PRRs are less critical for the outcome of Mtb infection. This is potentially due to redundancy of the numerous PRRs in the innate arsenal, such that Mtb rarely goes unnoticed. Genetic association studies investigating PRRs during Mtb infection should therefore be designed to investigate endophenotypes of infection – such as immunological or clinical variation – rather than just TB disease, if we hope to understand the molecular interface between innate immunity and Mtb. |
| first_indexed | 2024-12-18T02:12:27Z |
| format | Article |
| id | doaj.art-c306d3d714ef4ec8bee18dca66337d01 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-18T02:12:27Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-c306d3d714ef4ec8bee18dca66337d012022-12-21T21:24:28ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-06-011210.3389/fimmu.2021.714808714808Underwhelming or Misunderstood? Genetic Variability of Pattern Recognition Receptors in Immune Responses and Resistance to Mycobacterium tuberculosisJean-Yves Dubé0Jean-Yves Dubé1Jean-Yves Dubé2Vinicius M. Fava3Vinicius M. Fava4Erwin Schurr5Erwin Schurr6Erwin Schurr7Erwin Schurr8Erwin Schurr9Marcel A. Behr10Marcel A. Behr11Marcel A. Behr12Marcel A. Behr13Department of Microbiology and Immunology, McGill University, Montreal, QC, CanadaProgram in Infectious Diseases and Immunity in Global Health, The Research Institute of the McGill University Health Centre, Montreal, QC, CanadaMcGill International TB Centre, McGill University, Montreal, QC, CanadaProgram in Infectious Diseases and Immunity in Global Health, The Research Institute of the McGill University Health Centre, Montreal, QC, CanadaMcGill International TB Centre, McGill University, Montreal, QC, CanadaDepartment of Microbiology and Immunology, McGill University, Montreal, QC, CanadaProgram in Infectious Diseases and Immunity in Global Health, The Research Institute of the McGill University Health Centre, Montreal, QC, CanadaMcGill International TB Centre, McGill University, Montreal, QC, CanadaDepartment of Human Genetics, Faculty of Medicine, McGill University, Montreal, QC, CanadaDepartment of Medicine, Faculty of Medicine, McGill University, Montreal, QC, CanadaDepartment of Microbiology and Immunology, McGill University, Montreal, QC, CanadaProgram in Infectious Diseases and Immunity in Global Health, The Research Institute of the McGill University Health Centre, Montreal, QC, CanadaMcGill International TB Centre, McGill University, Montreal, QC, CanadaDepartment of Medicine, Faculty of Medicine, McGill University, Montreal, QC, CanadaHuman genetic control is thought to affect a considerable part of the outcome of infection with Mycobacterium tuberculosis (Mtb). Most of us deal with the pathogen by containment (associated with clinical “latency”) or sterilization, but tragically millions each year do not. After decades of studies on host genetic susceptibility to Mtb infection, genetic variation has been discovered to play a role in tuberculous immunoreactivity and tuberculosis (TB) disease. Genes encoding pattern recognition receptors (PRRs) enable a consistent, molecularly direct interaction between humans and Mtb which suggests the potential for co-evolution. In this review, we explore the roles ascribed to PRRs during Mtb infection and ask whether such a longstanding and intimate interface between our immune system and this pathogen plays a critical role in determining the outcome of Mtb infection. The scientific evidence to date suggests that PRR variation is clearly implicated in altered immunity to Mtb but has a more subtle role in limiting the pathogen and pathogenesis. In contrast to ‘effectors’ like IFN-γ, IL-12, Nitric Oxide and TNF that are critical for Mtb control, ‘sensors’ like PRRs are less critical for the outcome of Mtb infection. This is potentially due to redundancy of the numerous PRRs in the innate arsenal, such that Mtb rarely goes unnoticed. Genetic association studies investigating PRRs during Mtb infection should therefore be designed to investigate endophenotypes of infection – such as immunological or clinical variation – rather than just TB disease, if we hope to understand the molecular interface between innate immunity and Mtb.https://www.frontiersin.org/articles/10.3389/fimmu.2021.714808/fullmycobacterium tuberculosistuberculosispattern recognition receptor (PRR)genetic association studies (GAS)C-type lectin receptors (CLRs)NOD-like receptors (NLRs) |
| spellingShingle | Jean-Yves Dubé Jean-Yves Dubé Jean-Yves Dubé Vinicius M. Fava Vinicius M. Fava Erwin Schurr Erwin Schurr Erwin Schurr Erwin Schurr Erwin Schurr Marcel A. Behr Marcel A. Behr Marcel A. Behr Marcel A. Behr Underwhelming or Misunderstood? Genetic Variability of Pattern Recognition Receptors in Immune Responses and Resistance to Mycobacterium tuberculosis Frontiers in Immunology mycobacterium tuberculosis tuberculosis pattern recognition receptor (PRR) genetic association studies (GAS) C-type lectin receptors (CLRs) NOD-like receptors (NLRs) |
| title | Underwhelming or Misunderstood? Genetic Variability of Pattern Recognition Receptors in Immune Responses and Resistance to Mycobacterium tuberculosis |
| title_full | Underwhelming or Misunderstood? Genetic Variability of Pattern Recognition Receptors in Immune Responses and Resistance to Mycobacterium tuberculosis |
| title_fullStr | Underwhelming or Misunderstood? Genetic Variability of Pattern Recognition Receptors in Immune Responses and Resistance to Mycobacterium tuberculosis |
| title_full_unstemmed | Underwhelming or Misunderstood? Genetic Variability of Pattern Recognition Receptors in Immune Responses and Resistance to Mycobacterium tuberculosis |
| title_short | Underwhelming or Misunderstood? Genetic Variability of Pattern Recognition Receptors in Immune Responses and Resistance to Mycobacterium tuberculosis |
| title_sort | underwhelming or misunderstood genetic variability of pattern recognition receptors in immune responses and resistance to mycobacterium tuberculosis |
| topic | mycobacterium tuberculosis tuberculosis pattern recognition receptor (PRR) genetic association studies (GAS) C-type lectin receptors (CLRs) NOD-like receptors (NLRs) |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.714808/full |
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