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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...

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Autores principales: Pavletič, Miša, Korva, Misa, Knap, Nataša, Bogovič, Petra, Lusa, Lara, Strle, Klemen, Nahtigal Klevišar, Mirijam, Vovko, Tomaž, Tomažič, Janez, Lotrič-Furlan, Stanka, Strle, Franc, Avšič-Županc, Tatjana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281926/
https://www.ncbi.nlm.nih.gov/pubmed/34277474
http://dx.doi.org/10.3389/fcimb.2021.696337
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author Pavletič, Miša
Korva, Misa
Knap, Nataša
Bogovič, Petra
Lusa, Lara
Strle, Klemen
Nahtigal Klevišar, Mirijam
Vovko, Tomaž
Tomažič, Janez
Lotrič-Furlan, Stanka
Strle, Franc
Avšič-Županc, Tatjana
author_facet Pavletič, Miša
Korva, Misa
Knap, Nataša
Bogovič, Petra
Lusa, Lara
Strle, Klemen
Nahtigal Klevišar, Mirijam
Vovko, Tomaž
Tomažič, Janez
Lotrič-Furlan, Stanka
Strle, Franc
Avšič-Županc, Tatjana
author_sort Pavletič, Miša
collection PubMed
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.
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spelling pubmed-82819262021-07-16 Upregulated Intrathecal Expression of VEGF-A and Long Lasting Global Upregulation of Proinflammatory Immune Mediators in Vaccine Breakthrough Tick-Borne Encephalitis Pavletič, Miša Korva, Misa Knap, Nataša Bogovič, Petra Lusa, Lara Strle, Klemen Nahtigal Klevišar, Mirijam Vovko, Tomaž Tomažič, Janez Lotrič-Furlan, Stanka Strle, Franc Avšič-Županc, Tatjana Front Cell Infect Microbiol Cellular and Infection Microbiology 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. Frontiers Media S.A. 2021-07-01 /pmc/articles/PMC8281926/ /pubmed/34277474 http://dx.doi.org/10.3389/fcimb.2021.696337 Text en Copyright © 2021 Pavletič, Korva, Knap, Bogovič, Lusa, Strle, Nahtigal Klevišar, Vovko, Tomažič, Lotrič-Furlan, Strle and Avšič-Županc https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Pavletič, Miša
Korva, Misa
Knap, Nataša
Bogovič, Petra
Lusa, Lara
Strle, Klemen
Nahtigal Klevišar, Mirijam
Vovko, Tomaž
Tomažič, Janez
Lotrič-Furlan, Stanka
Strle, Franc
Avšič-Županc, Tatjana
Upregulated Intrathecal Expression of VEGF-A and Long Lasting Global Upregulation of Proinflammatory Immune Mediators in Vaccine Breakthrough Tick-Borne Encephalitis
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 Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281926/
https://www.ncbi.nlm.nih.gov/pubmed/34277474
http://dx.doi.org/10.3389/fcimb.2021.696337
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