Immune Responses in the Central Nervous System Are Anatomically Segregated in a Non-Human Primate Model of Human Immunodeficiency Virus Infection
The human immunodeficiency virus (HIV) accesses the central nervous system (CNS) early during infection, leading to HIV-associated cognitive impairment and establishment of a viral reservoir. Here, we describe a dichotomy in inflammatory responses in different CNS regions in simian immunodeficiency...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.00361/full |
| _version_ | 1819018342553354240 |
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| author | Barbara Tavano Vicky Tsipouri Gareth A. D. Hardy Caroline M. Royle Michael R. Keegan Michael R. Keegan Dietmar Fuchs Steven Patterson Neil Almond Neil Berry Claire Ham Deborah Ferguson Adriano Boasso |
| author_facet | Barbara Tavano Vicky Tsipouri Gareth A. D. Hardy Caroline M. Royle Michael R. Keegan Michael R. Keegan Dietmar Fuchs Steven Patterson Neil Almond Neil Berry Claire Ham Deborah Ferguson Adriano Boasso |
| author_sort | Barbara Tavano |
| collection | DOAJ |
| description | The human immunodeficiency virus (HIV) accesses the central nervous system (CNS) early during infection, leading to HIV-associated cognitive impairment and establishment of a viral reservoir. Here, we describe a dichotomy in inflammatory responses in different CNS regions in simian immunodeficiency virus (SIV)-infected macaques, a model for HIV infection. We found increased expression of inflammatory genes and perivascular leukocyte infiltration in the midbrain of SIV-infected macaques. Conversely, the frontal lobe showed downregulation of inflammatory genes associated with interferon-γ and interleukin-6 pathways, and absence of perivascular cuffing. These immunologic alterations were not accompanied by differences in SIV transcriptional activity within the tissue. Altered expression of genes associated with neurotoxicity was observed in both midbrain and frontal lobe. The segregation of inflammatory responses to specific regions of the CNS may both account for HIV-associated neurological symptoms and constitute a critical hurdle for HIV eradication by shielding the CNS viral reservoir from antiviral immunity. |
| first_indexed | 2024-12-21T03:17:54Z |
| format | Article |
| id | doaj.art-059140a26240458491a5e6fb9961998f |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-21T03:17:54Z |
| publishDate | 2017-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-059140a26240458491a5e6fb9961998f2022-12-21T19:17:47ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-03-01810.3389/fimmu.2017.00361238517Immune Responses in the Central Nervous System Are Anatomically Segregated in a Non-Human Primate Model of Human Immunodeficiency Virus InfectionBarbara Tavano0Vicky Tsipouri1Gareth A. D. Hardy2Caroline M. Royle3Michael R. Keegan4Michael R. Keegan5Dietmar Fuchs6Steven Patterson7Neil Almond8Neil Berry9Claire Ham10Deborah Ferguson11Adriano Boasso12Centre for Immunology and Vaccinology (CIV), Imperial College London, Chelsea and Westminster Hospital, London, UKNIHR Biological Research Unit, Royal Brompton Hospital, London, UKCentre for Immunology and Vaccinology (CIV), Imperial College London, Chelsea and Westminster Hospital, London, UKCentre for Immunology and Vaccinology (CIV), Imperial College London, Chelsea and Westminster Hospital, London, UKCentre for Immunology and Vaccinology (CIV), Imperial College London, Chelsea and Westminster Hospital, London, UKViiV Healthcare, Middlesex, UKDivision of Biological Chemistry, Biocenter, Innsbruck Medical University, Innsbruck, AustriaCentre for Immunology and Vaccinology (CIV), Imperial College London, Chelsea and Westminster Hospital, London, UKDivision of Virology, National Institute for Biological Standards and Controls (NIBSC), Potters Bar, Hertfordshire, UKDivision of Virology, National Institute for Biological Standards and Controls (NIBSC), Potters Bar, Hertfordshire, UKDivision of Virology, National Institute for Biological Standards and Controls (NIBSC), Potters Bar, Hertfordshire, UKDivision of Virology, National Institute for Biological Standards and Controls (NIBSC), Potters Bar, Hertfordshire, UKCentre for Immunology and Vaccinology (CIV), Imperial College London, Chelsea and Westminster Hospital, London, UKThe human immunodeficiency virus (HIV) accesses the central nervous system (CNS) early during infection, leading to HIV-associated cognitive impairment and establishment of a viral reservoir. Here, we describe a dichotomy in inflammatory responses in different CNS regions in simian immunodeficiency virus (SIV)-infected macaques, a model for HIV infection. We found increased expression of inflammatory genes and perivascular leukocyte infiltration in the midbrain of SIV-infected macaques. Conversely, the frontal lobe showed downregulation of inflammatory genes associated with interferon-γ and interleukin-6 pathways, and absence of perivascular cuffing. These immunologic alterations were not accompanied by differences in SIV transcriptional activity within the tissue. Altered expression of genes associated with neurotoxicity was observed in both midbrain and frontal lobe. The segregation of inflammatory responses to specific regions of the CNS may both account for HIV-associated neurological symptoms and constitute a critical hurdle for HIV eradication by shielding the CNS viral reservoir from antiviral immunity.http://journal.frontiersin.org/article/10.3389/fimmu.2017.00361/fullsimian immunodeficiency viruscentral nervous systemneuroinflammationneurotoxicityindoleamine (2,3)-dioxygenase |
| spellingShingle | Barbara Tavano Vicky Tsipouri Gareth A. D. Hardy Caroline M. Royle Michael R. Keegan Michael R. Keegan Dietmar Fuchs Steven Patterson Neil Almond Neil Berry Claire Ham Deborah Ferguson Adriano Boasso Immune Responses in the Central Nervous System Are Anatomically Segregated in a Non-Human Primate Model of Human Immunodeficiency Virus Infection Frontiers in Immunology simian immunodeficiency virus central nervous system neuroinflammation neurotoxicity indoleamine (2,3)-dioxygenase |
| title | Immune Responses in the Central Nervous System Are Anatomically Segregated in a Non-Human Primate Model of Human Immunodeficiency Virus Infection |
| title_full | Immune Responses in the Central Nervous System Are Anatomically Segregated in a Non-Human Primate Model of Human Immunodeficiency Virus Infection |
| title_fullStr | Immune Responses in the Central Nervous System Are Anatomically Segregated in a Non-Human Primate Model of Human Immunodeficiency Virus Infection |
| title_full_unstemmed | Immune Responses in the Central Nervous System Are Anatomically Segregated in a Non-Human Primate Model of Human Immunodeficiency Virus Infection |
| title_short | Immune Responses in the Central Nervous System Are Anatomically Segregated in a Non-Human Primate Model of Human Immunodeficiency Virus Infection |
| title_sort | immune responses in the central nervous system are anatomically segregated in a non human primate model of human immunodeficiency virus infection |
| topic | simian immunodeficiency virus central nervous system neuroinflammation neurotoxicity indoleamine (2,3)-dioxygenase |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2017.00361/full |
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