Adaptive and Innate Immune Cells in Fetal Human Cytomegalovirus-Infected Brains
Background: The understanding of the pathogenesis of cytomegalovirus (CMV)-induced fetal brain lesions is limited. We aimed to quantify adaptive and innate immune cells and CMV-infected cells in fetal brains with various degrees of brain damage. Methods: In total, 26 archived embedded fetal brains w...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-01-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/8/2/176 |
| _version_ | 1818160486514950144 |
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| author | Yann Sellier Florence Marliot Bettina Bessières Julien Stirnemann Ferechte Encha-Razavi Tiffany Guilleminot Nacilla Haicheur Franck Pages Yves Ville Marianne Leruez-Ville |
| author_facet | Yann Sellier Florence Marliot Bettina Bessières Julien Stirnemann Ferechte Encha-Razavi Tiffany Guilleminot Nacilla Haicheur Franck Pages Yves Ville Marianne Leruez-Ville |
| author_sort | Yann Sellier |
| collection | DOAJ |
| description | Background: The understanding of the pathogenesis of cytomegalovirus (CMV)-induced fetal brain lesions is limited. We aimed to quantify adaptive and innate immune cells and CMV-infected cells in fetal brains with various degrees of brain damage. Methods: In total, 26 archived embedded fetal brains were studied, of which 21 were CMV-infected and classified in severely affected (<i>n</i> = 13) and moderately affected (<i>n</i> = 8), and 5 were uninfected controls. The respective magnitude of infected cells, immune cells (CD8<sup>+</sup>, B cells, plasma cells, NK cells, and macrophages), and expression of immune checkpoint receptors (PD-1/PD-L1 and LAG-3) were measured by immunochemistry and quantified by quantitative imaging analysis. Results: Quantities of CD8<sup>+</sup>, plasma cells, NK cells, macrophages, and HCMV<sup>+</sup> cells and expression of PD-1/PD-L1 and LAG-3 were significantly higher in severely affected than in moderately affected brains (all <i>p</i> values < 0.05). A strong link between higher number of stained cells for HCMV/CD8 and PD-1 and severity of brain lesions was found by component analysis. Conclusions: The higher expression of CD8, PD-1, and LAG-3 in severely affected brains could reflect immune exhaustion of cerebral T cells. These exhausted T cells could be ineffective in controlling viral multiplication itself, leading to more severe brain lesions. The study of the functionality of brain leucocytes ex vivo is needed to confirm this hypothesis. |
| first_indexed | 2024-12-11T16:02:39Z |
| format | Article |
| id | doaj.art-74d3bab1560448df9cad531fee8e3df2 |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-12-11T16:02:39Z |
| publishDate | 2020-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-74d3bab1560448df9cad531fee8e3df22022-12-22T00:59:17ZengMDPI AGMicroorganisms2076-26072020-01-018217610.3390/microorganisms8020176microorganisms8020176Adaptive and Innate Immune Cells in Fetal Human Cytomegalovirus-Infected BrainsYann Sellier0Florence Marliot1Bettina Bessières2Julien Stirnemann3Ferechte Encha-Razavi4Tiffany Guilleminot5Nacilla Haicheur6Franck Pages7Yves Ville8Marianne Leruez-Ville9Service de Gynécologie-Obstétrique, Hôpital Universitaire Necker-Enfants-malades, AP-HP, 149 rue de Sèvres, 75015 Paris, FranceUniversité Paris Descartes, Sorbonne Paris Cité, 75015 Paris, FranceUniversité Paris Descartes, Sorbonne Paris Cité, 75015 Paris, FranceService de Gynécologie-Obstétrique, Hôpital Universitaire Necker-Enfants-malades, AP-HP, 149 rue de Sèvres, 75015 Paris, FranceUniversité Paris Descartes, Sorbonne Paris Cité, 75015 Paris, FranceUniversité Paris Descartes, Sorbonne Paris Cité, 75015 Paris, FranceINSERM U872, plateforme d’Immuno-monitoring, service d’Immunologie Biologique, Hôpital Européen Georges-Pompidou, AP-HP, 75015 Paris, FranceUniversité Paris Descartes, Sorbonne Paris Cité, 75015 Paris, FranceService de Gynécologie-Obstétrique, Hôpital Universitaire Necker-Enfants-malades, AP-HP, 149 rue de Sèvres, 75015 Paris, FranceEHU 7328 PACT, 75015 Paris, FranceBackground: The understanding of the pathogenesis of cytomegalovirus (CMV)-induced fetal brain lesions is limited. We aimed to quantify adaptive and innate immune cells and CMV-infected cells in fetal brains with various degrees of brain damage. Methods: In total, 26 archived embedded fetal brains were studied, of which 21 were CMV-infected and classified in severely affected (<i>n</i> = 13) and moderately affected (<i>n</i> = 8), and 5 were uninfected controls. The respective magnitude of infected cells, immune cells (CD8<sup>+</sup>, B cells, plasma cells, NK cells, and macrophages), and expression of immune checkpoint receptors (PD-1/PD-L1 and LAG-3) were measured by immunochemistry and quantified by quantitative imaging analysis. Results: Quantities of CD8<sup>+</sup>, plasma cells, NK cells, macrophages, and HCMV<sup>+</sup> cells and expression of PD-1/PD-L1 and LAG-3 were significantly higher in severely affected than in moderately affected brains (all <i>p</i> values < 0.05). A strong link between higher number of stained cells for HCMV/CD8 and PD-1 and severity of brain lesions was found by component analysis. Conclusions: The higher expression of CD8, PD-1, and LAG-3 in severely affected brains could reflect immune exhaustion of cerebral T cells. These exhausted T cells could be ineffective in controlling viral multiplication itself, leading to more severe brain lesions. The study of the functionality of brain leucocytes ex vivo is needed to confirm this hypothesis.https://www.mdpi.com/2076-2607/8/2/176cytomegalovirusfetal brainpd-1lag-3exhaustionimmune cells |
| spellingShingle | Yann Sellier Florence Marliot Bettina Bessières Julien Stirnemann Ferechte Encha-Razavi Tiffany Guilleminot Nacilla Haicheur Franck Pages Yves Ville Marianne Leruez-Ville Adaptive and Innate Immune Cells in Fetal Human Cytomegalovirus-Infected Brains Microorganisms cytomegalovirus fetal brain pd-1 lag-3 exhaustion immune cells |
| title | Adaptive and Innate Immune Cells in Fetal Human Cytomegalovirus-Infected Brains |
| title_full | Adaptive and Innate Immune Cells in Fetal Human Cytomegalovirus-Infected Brains |
| title_fullStr | Adaptive and Innate Immune Cells in Fetal Human Cytomegalovirus-Infected Brains |
| title_full_unstemmed | Adaptive and Innate Immune Cells in Fetal Human Cytomegalovirus-Infected Brains |
| title_short | Adaptive and Innate Immune Cells in Fetal Human Cytomegalovirus-Infected Brains |
| title_sort | adaptive and innate immune cells in fetal human cytomegalovirus infected brains |
| topic | cytomegalovirus fetal brain pd-1 lag-3 exhaustion immune cells |
| url | https://www.mdpi.com/2076-2607/8/2/176 |
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