Influenza A virus elicits peri-vascular adipose tissue inflammation and vascular dysfunction of the aorta in pregnant mice.
Influenza A virus (IAV) infection during pregnancy initiates significant aortic endothelial and vascular smooth muscle dysfunction, with inflammation and T cell activation, but the details of the mechanism are yet to be clearly defined. Here we demonstrate that IAV disseminates preferentially into t...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-08-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1010703 |
| _version_ | 1828144877704052736 |
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| author | Osezua Oseghale Stella Liong Madison Coward-Smith Eunice E To Jonathan R Erlich Raymond Luong Felicia Liong Mark Miles Shaghayegh Norouzi Cara Martin Sharon O'Toole Robert D Brooks Steven Bozinovski Ross Vlahos John J O'Leary Doug A Brooks Stavros Selemidis |
| author_facet | Osezua Oseghale Stella Liong Madison Coward-Smith Eunice E To Jonathan R Erlich Raymond Luong Felicia Liong Mark Miles Shaghayegh Norouzi Cara Martin Sharon O'Toole Robert D Brooks Steven Bozinovski Ross Vlahos John J O'Leary Doug A Brooks Stavros Selemidis |
| author_sort | Osezua Oseghale |
| collection | DOAJ |
| description | Influenza A virus (IAV) infection during pregnancy initiates significant aortic endothelial and vascular smooth muscle dysfunction, with inflammation and T cell activation, but the details of the mechanism are yet to be clearly defined. Here we demonstrate that IAV disseminates preferentially into the perivascular adipose tissue (PVAT) of the aorta in mice. IAV mRNA levels in the PVAT increased at 1-3 days post infection (d.p.i) with the levels being ~4-8 fold higher compared with the vessel wall. IAV infection also increased Ly6Clow patrolling monocytes and Ly6Chigh pro-inflammatory monocytes in the vessel wall at 3 d.p.i., which was then followed by a greater homing of these monocytes into the PVAT at 6 d.p.i. The vascular immune phenotype was characteristic of a "vascular storm"- like response, with increases in neutrophils, pro-inflammatory cytokines and oxidative stress markers in the PVAT and arterial wall, which was associated with an impairment in endothelium-dependent relaxation to acetylcholine. IAV also triggered a PVAT compartmentalised elevation in CD4+ and CD8+ activated T cells. In conclusion, the PVAT of the aorta is a niche that supports IAV dissemination and a site for perpetuating a profound innate inflammatory and adaptive T cell response. The manifestation of this inflammatory response in the PVAT following IAV infection may be central to the genesis of cardiovascular complications arising during pregnancy. |
| first_indexed | 2024-04-11T20:23:52Z |
| format | Article |
| id | doaj.art-87939b1b8d0043309e5d3dfd59bd4e58 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-04-11T20:23:52Z |
| publishDate | 2022-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-87939b1b8d0043309e5d3dfd59bd4e582022-12-22T04:04:43ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742022-08-01188e101070310.1371/journal.ppat.1010703Influenza A virus elicits peri-vascular adipose tissue inflammation and vascular dysfunction of the aorta in pregnant mice.Osezua OseghaleStella LiongMadison Coward-SmithEunice E ToJonathan R ErlichRaymond LuongFelicia LiongMark MilesShaghayegh NorouziCara MartinSharon O'TooleRobert D BrooksSteven BozinovskiRoss VlahosJohn J O'LearyDoug A BrooksStavros SelemidisInfluenza A virus (IAV) infection during pregnancy initiates significant aortic endothelial and vascular smooth muscle dysfunction, with inflammation and T cell activation, but the details of the mechanism are yet to be clearly defined. Here we demonstrate that IAV disseminates preferentially into the perivascular adipose tissue (PVAT) of the aorta in mice. IAV mRNA levels in the PVAT increased at 1-3 days post infection (d.p.i) with the levels being ~4-8 fold higher compared with the vessel wall. IAV infection also increased Ly6Clow patrolling monocytes and Ly6Chigh pro-inflammatory monocytes in the vessel wall at 3 d.p.i., which was then followed by a greater homing of these monocytes into the PVAT at 6 d.p.i. The vascular immune phenotype was characteristic of a "vascular storm"- like response, with increases in neutrophils, pro-inflammatory cytokines and oxidative stress markers in the PVAT and arterial wall, which was associated with an impairment in endothelium-dependent relaxation to acetylcholine. IAV also triggered a PVAT compartmentalised elevation in CD4+ and CD8+ activated T cells. In conclusion, the PVAT of the aorta is a niche that supports IAV dissemination and a site for perpetuating a profound innate inflammatory and adaptive T cell response. The manifestation of this inflammatory response in the PVAT following IAV infection may be central to the genesis of cardiovascular complications arising during pregnancy.https://doi.org/10.1371/journal.ppat.1010703 |
| spellingShingle | Osezua Oseghale Stella Liong Madison Coward-Smith Eunice E To Jonathan R Erlich Raymond Luong Felicia Liong Mark Miles Shaghayegh Norouzi Cara Martin Sharon O'Toole Robert D Brooks Steven Bozinovski Ross Vlahos John J O'Leary Doug A Brooks Stavros Selemidis Influenza A virus elicits peri-vascular adipose tissue inflammation and vascular dysfunction of the aorta in pregnant mice. PLoS Pathogens |
| title | Influenza A virus elicits peri-vascular adipose tissue inflammation and vascular dysfunction of the aorta in pregnant mice. |
| title_full | Influenza A virus elicits peri-vascular adipose tissue inflammation and vascular dysfunction of the aorta in pregnant mice. |
| title_fullStr | Influenza A virus elicits peri-vascular adipose tissue inflammation and vascular dysfunction of the aorta in pregnant mice. |
| title_full_unstemmed | Influenza A virus elicits peri-vascular adipose tissue inflammation and vascular dysfunction of the aorta in pregnant mice. |
| title_short | Influenza A virus elicits peri-vascular adipose tissue inflammation and vascular dysfunction of the aorta in pregnant mice. |
| title_sort | influenza a virus elicits peri vascular adipose tissue inflammation and vascular dysfunction of the aorta in pregnant mice |
| url | https://doi.org/10.1371/journal.ppat.1010703 |
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