Live imaging of microglia during sleeping sickness reveals early and heterogeneous inflammatory responses
IntroductionInvasion of the central nervous system (CNS) is the most serious consequence of Trypanosoma brucei infection, which causes sleeping sickness. Recent experimental data have revealed some more insights into the disease during the meningoencephalitic stage. However, detailed cellular proces...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1253648/full |
| _version_ | 1797687096080596992 |
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| author | Nestor L. Uzcategui Nestor L. Uzcategui Nestor L. Uzcategui Sena Güçer Cris Richter Annika Speidel Elizabeta Zirdum Michael Duszenko Olga Garaschuk Katherine Figarella |
| author_facet | Nestor L. Uzcategui Nestor L. Uzcategui Nestor L. Uzcategui Sena Güçer Cris Richter Annika Speidel Elizabeta Zirdum Michael Duszenko Olga Garaschuk Katherine Figarella |
| author_sort | Nestor L. Uzcategui |
| collection | DOAJ |
| description | IntroductionInvasion of the central nervous system (CNS) is the most serious consequence of Trypanosoma brucei infection, which causes sleeping sickness. Recent experimental data have revealed some more insights into the disease during the meningoencephalitic stage. However, detailed cellular processes befalling the CNS during the disease are poorly understood.MethodsTo further address this issue, we implanted a cranial window on the cortex of B6.129P2(Cg)-Cx3cr1tm1Litt/J mice, infected them with Trypanosoma brucei expressing RFP via intraperitoneal injection, and monitored microglial cells and parasites longitudinally over 30 days using in vivo 2-photon imaging. We correlated the observed changes with histological analyses to evaluate the recruitment of peripheral immune cells.Results and discussionWe uncovered an early involvement of microglia that precedes invasion of the CNS by the parasite. We accomplished a detailed characterization of the progressive sequence of events that correlates with microglial morphological changes and microgliosis. Our findings unveiled a heterogeneous microglial response in places of initial homeostatic disruption near brain barriers and pointed out an exceptional capability of microglia to hamper parasite proliferation inside the brain. We also found early signs of inflammation in the meninges, which synchronize with the microglial response. Moreover, we observed a massive infiltration of peripheral immune cells into the parenchyma as a signature in the final disease stage. Overall, our study provides new insights into the host-pathogen immune interactions in the meningeal and parenchymal compartments of the neocortex. |
| first_indexed | 2024-03-12T01:13:23Z |
| format | Article |
| id | doaj.art-0f9fbc8aa1e74858aca4939bec30f804 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-12T01:13:23Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-0f9fbc8aa1e74858aca4939bec30f8042023-09-13T21:35:44ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-09-011410.3389/fimmu.2023.12536481253648Live imaging of microglia during sleeping sickness reveals early and heterogeneous inflammatory responsesNestor L. Uzcategui0Nestor L. Uzcategui1Nestor L. Uzcategui2Sena Güçer3Cris Richter4Annika Speidel5Elizabeta Zirdum6Michael Duszenko7Olga Garaschuk8Katherine Figarella9Department of Neurophysiology, Institute of Physiology, University of Tuebingen, Tuebingen, GermanyInstitute of Tropical Medicine, University of Tuebingen, Tuebingen, GermanyInstitute of Anatomy, Central University of Venezuela, Caracas, VenezuelaDepartment of Neurophysiology, Institute of Physiology, University of Tuebingen, Tuebingen, GermanyDepartment of Neurophysiology, Institute of Physiology, University of Tuebingen, Tuebingen, GermanyDepartment of Neurophysiology, Institute of Physiology, University of Tuebingen, Tuebingen, GermanyDepartment of Neurophysiology, Institute of Physiology, University of Tuebingen, Tuebingen, GermanyDepartment of Neurophysiology, Institute of Physiology, University of Tuebingen, Tuebingen, GermanyDepartment of Neurophysiology, Institute of Physiology, University of Tuebingen, Tuebingen, GermanyDepartment of Neurophysiology, Institute of Physiology, University of Tuebingen, Tuebingen, GermanyIntroductionInvasion of the central nervous system (CNS) is the most serious consequence of Trypanosoma brucei infection, which causes sleeping sickness. Recent experimental data have revealed some more insights into the disease during the meningoencephalitic stage. However, detailed cellular processes befalling the CNS during the disease are poorly understood.MethodsTo further address this issue, we implanted a cranial window on the cortex of B6.129P2(Cg)-Cx3cr1tm1Litt/J mice, infected them with Trypanosoma brucei expressing RFP via intraperitoneal injection, and monitored microglial cells and parasites longitudinally over 30 days using in vivo 2-photon imaging. We correlated the observed changes with histological analyses to evaluate the recruitment of peripheral immune cells.Results and discussionWe uncovered an early involvement of microglia that precedes invasion of the CNS by the parasite. We accomplished a detailed characterization of the progressive sequence of events that correlates with microglial morphological changes and microgliosis. Our findings unveiled a heterogeneous microglial response in places of initial homeostatic disruption near brain barriers and pointed out an exceptional capability of microglia to hamper parasite proliferation inside the brain. We also found early signs of inflammation in the meninges, which synchronize with the microglial response. Moreover, we observed a massive infiltration of peripheral immune cells into the parenchyma as a signature in the final disease stage. Overall, our study provides new insights into the host-pathogen immune interactions in the meningeal and parenchymal compartments of the neocortex.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1253648/fullTrypanosoma bruceimicrogliameningesinflammationheterogeneous responseimmune cell recruitment |
| spellingShingle | Nestor L. Uzcategui Nestor L. Uzcategui Nestor L. Uzcategui Sena Güçer Cris Richter Annika Speidel Elizabeta Zirdum Michael Duszenko Olga Garaschuk Katherine Figarella Live imaging of microglia during sleeping sickness reveals early and heterogeneous inflammatory responses Frontiers in Immunology Trypanosoma brucei microglia meninges inflammation heterogeneous response immune cell recruitment |
| title | Live imaging of microglia during sleeping sickness reveals early and heterogeneous inflammatory responses |
| title_full | Live imaging of microglia during sleeping sickness reveals early and heterogeneous inflammatory responses |
| title_fullStr | Live imaging of microglia during sleeping sickness reveals early and heterogeneous inflammatory responses |
| title_full_unstemmed | Live imaging of microglia during sleeping sickness reveals early and heterogeneous inflammatory responses |
| title_short | Live imaging of microglia during sleeping sickness reveals early and heterogeneous inflammatory responses |
| title_sort | live imaging of microglia during sleeping sickness reveals early and heterogeneous inflammatory responses |
| topic | Trypanosoma brucei microglia meninges inflammation heterogeneous response immune cell recruitment |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1253648/full |
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