Upregulated Intrathecal Expression of VEGF-A and Long Lasting Global Upregulation of Proinflammatory Immune Mediators in Vaccine Breakthrough Tick-Borne Encephalitis
Although anti-TBE vaccines are highly effective, vaccine breakthrough (VBT) cases have been reported. With increasing evidence for immune system involvement in TBE pathogenesis, we characterized the immune mediators reflecting innate and adaptive T and B cell responses in neurological and convalesce...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-07-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2021.696337/full |
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| author | Miša Pavletič Misa Korva Nataša Knap Petra Bogovič Lara Lusa Lara Lusa Klemen Strle Mirijam Nahtigal Klevišar Tomaž Vovko Janez Tomažič Stanka Lotrič-Furlan Franc Strle Tatjana Avšič-Županc |
| author_facet | Miša Pavletič Misa Korva Nataša Knap Petra Bogovič Lara Lusa Lara Lusa Klemen Strle Mirijam Nahtigal Klevišar Tomaž Vovko Janez Tomažič Stanka Lotrič-Furlan Franc Strle Tatjana Avšič-Županc |
| author_sort | Miša Pavletič |
| collection | DOAJ |
| description | Although anti-TBE vaccines are highly effective, vaccine breakthrough (VBT) cases have been reported. With increasing evidence for immune system involvement in TBE pathogenesis, we characterized the immune mediators reflecting innate and adaptive T and B cell responses in neurological and convalescent phase in VBT TBE patients. At the beginning of the neurological phase, VBT patients have significantly higher serum levels of several innate and adaptive inflammatory cytokines compared to healthy donors, reflecting a global inflammatory state. The majority of cytokines, particularly those associated with innate and Th1 responses, are highly concentrated in CSF and positively correlate with intrathecal immune cell counts, demonstrating the localization of Th1 and proinflammatory responses in CNS, the site of disease in TBE. Interestingly, compared to unvaccinated TBE patients, VBT TBE patients have significantly higher CSF levels of VEGF-A and IFN-β and higher systemic levels of neutrophil chemoattractants IL-8/CXCL8 and GROα/CXCL1 on admission. Moreover, serum levels of IL-8/CXCL8 and GROα/CXCL1 remain elevated for two months after the onset of neurological symptoms, indicating a prolonged systemic immune activation in VBT patients. These findings provide the first insights into the type of immune responses and their dynamics during TBE in VBT patients. An observed systemic upregulation of neutrophil derived inflammation in acute and convalescent phase of TBE together with highly expressed VEGF-A could contribute to BBB disruption that facilitates the entry of immune cells and supports the intrathecal localization of Th1 responses observed in VBT patients. |
| first_indexed | 2024-12-14T17:16:20Z |
| format | Article |
| id | doaj.art-48a9332ebbea460bbeef03b9ee8a3d18 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-14T17:16:20Z |
| publishDate | 2021-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-48a9332ebbea460bbeef03b9ee8a3d182022-12-21T22:53:25ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882021-07-011110.3389/fcimb.2021.696337696337Upregulated Intrathecal Expression of VEGF-A and Long Lasting Global Upregulation of Proinflammatory Immune Mediators in Vaccine Breakthrough Tick-Borne EncephalitisMiša Pavletič0Misa Korva1Nataša Knap2Petra Bogovič3Lara Lusa4Lara Lusa5Klemen Strle6Mirijam Nahtigal Klevišar7Tomaž Vovko8Janez Tomažič9Stanka Lotrič-Furlan10Franc Strle11Tatjana Avšič-Županc12Laboratory for Diagnostic of Zoonoses and World Health Organization (WHO) Center, Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, SloveniaLaboratory for Diagnostic of Zoonoses and World Health Organization (WHO) Center, Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, SloveniaLaboratory for Diagnostic of Zoonoses and World Health Organization (WHO) Center, Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, SloveniaDepartment of Infectious Diseases, University Medical Center Ljubljana, Ljubljana, SloveniaInstitute for Biostatistics and Medical Informatics, Faculty of Medicine, University of Ljubljana, Ljubljana, SloveniaDepartment of Mathematics, Faculty of Mathematics, Natural Sciences and Information Technologies, University of Primorska, Koper, SloveniaDivision of Infectious Diseases, Microbial Pathogenesis and Immunology Laboratory, Wadsworth Center, New York State (NYS) Department of Health, Albany, NY, United StatesDepartment of Infectious Diseases, University Medical Center Ljubljana, Ljubljana, SloveniaDepartment of Infectious Diseases, University Medical Center Ljubljana, Ljubljana, SloveniaDepartment of Infectious Diseases, University Medical Center Ljubljana, Ljubljana, SloveniaDepartment of Infectious Diseases, University Medical Center Ljubljana, Ljubljana, SloveniaDepartment of Infectious Diseases, University Medical Center Ljubljana, Ljubljana, SloveniaLaboratory for Diagnostic of Zoonoses and World Health Organization (WHO) Center, Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, SloveniaAlthough anti-TBE vaccines are highly effective, vaccine breakthrough (VBT) cases have been reported. With increasing evidence for immune system involvement in TBE pathogenesis, we characterized the immune mediators reflecting innate and adaptive T and B cell responses in neurological and convalescent phase in VBT TBE patients. At the beginning of the neurological phase, VBT patients have significantly higher serum levels of several innate and adaptive inflammatory cytokines compared to healthy donors, reflecting a global inflammatory state. The majority of cytokines, particularly those associated with innate and Th1 responses, are highly concentrated in CSF and positively correlate with intrathecal immune cell counts, demonstrating the localization of Th1 and proinflammatory responses in CNS, the site of disease in TBE. Interestingly, compared to unvaccinated TBE patients, VBT TBE patients have significantly higher CSF levels of VEGF-A and IFN-β and higher systemic levels of neutrophil chemoattractants IL-8/CXCL8 and GROα/CXCL1 on admission. Moreover, serum levels of IL-8/CXCL8 and GROα/CXCL1 remain elevated for two months after the onset of neurological symptoms, indicating a prolonged systemic immune activation in VBT patients. These findings provide the first insights into the type of immune responses and their dynamics during TBE in VBT patients. An observed systemic upregulation of neutrophil derived inflammation in acute and convalescent phase of TBE together with highly expressed VEGF-A could contribute to BBB disruption that facilitates the entry of immune cells and supports the intrathecal localization of Th1 responses observed in VBT patients.https://www.frontiersin.org/articles/10.3389/fcimb.2021.696337/fulltick-borne encephalitisvaccine breakthroughcytokineschemokinesproinflammatory responseVEGF |
| spellingShingle | Miša Pavletič Misa Korva Nataša Knap Petra Bogovič Lara Lusa Lara Lusa Klemen Strle Mirijam Nahtigal Klevišar Tomaž Vovko Janez Tomažič Stanka Lotrič-Furlan Franc Strle Tatjana Avšič-Županc Upregulated Intrathecal Expression of VEGF-A and Long Lasting Global Upregulation of Proinflammatory Immune Mediators in Vaccine Breakthrough Tick-Borne Encephalitis Frontiers in Cellular and Infection Microbiology tick-borne encephalitis vaccine breakthrough cytokines chemokines proinflammatory response VEGF |
| title | Upregulated Intrathecal Expression of VEGF-A and Long Lasting Global Upregulation of Proinflammatory Immune Mediators in Vaccine Breakthrough Tick-Borne Encephalitis |
| title_full | Upregulated Intrathecal Expression of VEGF-A and Long Lasting Global Upregulation of Proinflammatory Immune Mediators in Vaccine Breakthrough Tick-Borne Encephalitis |
| title_fullStr | Upregulated Intrathecal Expression of VEGF-A and Long Lasting Global Upregulation of Proinflammatory Immune Mediators in Vaccine Breakthrough Tick-Borne Encephalitis |
| title_full_unstemmed | Upregulated Intrathecal Expression of VEGF-A and Long Lasting Global Upregulation of Proinflammatory Immune Mediators in Vaccine Breakthrough Tick-Borne Encephalitis |
| title_short | Upregulated Intrathecal Expression of VEGF-A and Long Lasting Global Upregulation of Proinflammatory Immune Mediators in Vaccine Breakthrough Tick-Borne Encephalitis |
| title_sort | upregulated intrathecal expression of vegf a and long lasting global upregulation of proinflammatory immune mediators in vaccine breakthrough tick borne encephalitis |
| topic | tick-borne encephalitis vaccine breakthrough cytokines chemokines proinflammatory response VEGF |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2021.696337/full |
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