Cargando…
Effector CD8 T Cell-Dependent Zika Virus Control in the CNS: A Matter of Time and Numbers
Zika virus (ZIKV), a mosquito-borne flavivirus, came into the spotlight in 2016 when it was found to be associated with an increased rate of microcephalic newborns in Brazil. The virus has further been recognized to cause neurologic complications in children and adults in the form of myelitis, encep...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461798/ https://www.ncbi.nlm.nih.gov/pubmed/32973802 http://dx.doi.org/10.3389/fimmu.2020.01977 |
_version_ | 1783576792149262336 |
---|---|
author | Nazerai, Loulieta Schøller, Amalie Skak Bassi, Maria Rosaria Buus, Søren Stryhn, Anette Christensen, Jan Pravsgaard Thomsen, Allan Randrup |
author_facet | Nazerai, Loulieta Schøller, Amalie Skak Bassi, Maria Rosaria Buus, Søren Stryhn, Anette Christensen, Jan Pravsgaard Thomsen, Allan Randrup |
author_sort | Nazerai, Loulieta |
collection | PubMed |
description | Zika virus (ZIKV), a mosquito-borne flavivirus, came into the spotlight in 2016 when it was found to be associated with an increased rate of microcephalic newborns in Brazil. The virus has further been recognized to cause neurologic complications in children and adults in the form of myelitis, encephalitis, acute disseminated encephalomyelitis (ADEM) and Guillain Barre Syndrome in a fraction of infected individuals. With the ultimate goal of identifying correlates of protection to guide the design of an effective vaccine, the study of the immune response to ZIKV infection has become the focus of research worldwide. Both innate and adaptive immune responses seem to be essential for controlling the infection. Induction of sufficient levels of neutralizing antibodies has been strongly correlated with protection against reinfection in various models, while the role of CD8 T cells as antiviral effectors in the CNS has been controversial. In an attempt to improve our understanding regarding the role of ZIKV-induced CD8 T cells in protective immunity inside the CNS, we have expanded on previous studies in intracranially infected mice. In a recent study, we have demonstrated that, peripheral ZIKV infection in adult C57BL/6 mice induces a robust CD8 T cell response that peaks within a week. In the present study, we used B cell deficient as well as wild-type mice to show that there is a race between CXCR3-dependent recruitment of the effector CD8 T cells and local ZIKV replication, and that CD8 T cells are capable of local viral control if they arrive in the brain early after viral invasion, in appropriate numbers and differentiation state. Our data highlight the benefits of considering this subset when designing vaccines against Zika virus. |
format | Online Article Text |
id | pubmed-7461798 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-74617982020-09-23 Effector CD8 T Cell-Dependent Zika Virus Control in the CNS: A Matter of Time and Numbers Nazerai, Loulieta Schøller, Amalie Skak Bassi, Maria Rosaria Buus, Søren Stryhn, Anette Christensen, Jan Pravsgaard Thomsen, Allan Randrup Front Immunol Immunology Zika virus (ZIKV), a mosquito-borne flavivirus, came into the spotlight in 2016 when it was found to be associated with an increased rate of microcephalic newborns in Brazil. The virus has further been recognized to cause neurologic complications in children and adults in the form of myelitis, encephalitis, acute disseminated encephalomyelitis (ADEM) and Guillain Barre Syndrome in a fraction of infected individuals. With the ultimate goal of identifying correlates of protection to guide the design of an effective vaccine, the study of the immune response to ZIKV infection has become the focus of research worldwide. Both innate and adaptive immune responses seem to be essential for controlling the infection. Induction of sufficient levels of neutralizing antibodies has been strongly correlated with protection against reinfection in various models, while the role of CD8 T cells as antiviral effectors in the CNS has been controversial. In an attempt to improve our understanding regarding the role of ZIKV-induced CD8 T cells in protective immunity inside the CNS, we have expanded on previous studies in intracranially infected mice. In a recent study, we have demonstrated that, peripheral ZIKV infection in adult C57BL/6 mice induces a robust CD8 T cell response that peaks within a week. In the present study, we used B cell deficient as well as wild-type mice to show that there is a race between CXCR3-dependent recruitment of the effector CD8 T cells and local ZIKV replication, and that CD8 T cells are capable of local viral control if they arrive in the brain early after viral invasion, in appropriate numbers and differentiation state. Our data highlight the benefits of considering this subset when designing vaccines against Zika virus. Frontiers Media S.A. 2020-08-18 /pmc/articles/PMC7461798/ /pubmed/32973802 http://dx.doi.org/10.3389/fimmu.2020.01977 Text en Copyright © 2020 Nazerai, Schøller, Bassi, Buus, Stryhn, Christensen and Thomsen. http://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 | Immunology Nazerai, Loulieta Schøller, Amalie Skak Bassi, Maria Rosaria Buus, Søren Stryhn, Anette Christensen, Jan Pravsgaard Thomsen, Allan Randrup Effector CD8 T Cell-Dependent Zika Virus Control in the CNS: A Matter of Time and Numbers |
title | Effector CD8 T Cell-Dependent Zika Virus Control in the CNS: A Matter of Time and Numbers |
title_full | Effector CD8 T Cell-Dependent Zika Virus Control in the CNS: A Matter of Time and Numbers |
title_fullStr | Effector CD8 T Cell-Dependent Zika Virus Control in the CNS: A Matter of Time and Numbers |
title_full_unstemmed | Effector CD8 T Cell-Dependent Zika Virus Control in the CNS: A Matter of Time and Numbers |
title_short | Effector CD8 T Cell-Dependent Zika Virus Control in the CNS: A Matter of Time and Numbers |
title_sort | effector cd8 t cell-dependent zika virus control in the cns: a matter of time and numbers |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461798/ https://www.ncbi.nlm.nih.gov/pubmed/32973802 http://dx.doi.org/10.3389/fimmu.2020.01977 |
work_keys_str_mv | AT nazerailoulieta effectorcd8tcelldependentzikaviruscontrolinthecnsamatteroftimeandnumbers AT schølleramalieskak effectorcd8tcelldependentzikaviruscontrolinthecnsamatteroftimeandnumbers AT bassimariarosaria effectorcd8tcelldependentzikaviruscontrolinthecnsamatteroftimeandnumbers AT buussøren effectorcd8tcelldependentzikaviruscontrolinthecnsamatteroftimeandnumbers AT stryhnanette effectorcd8tcelldependentzikaviruscontrolinthecnsamatteroftimeandnumbers AT christensenjanpravsgaard effectorcd8tcelldependentzikaviruscontrolinthecnsamatteroftimeandnumbers AT thomsenallanrandrup effectorcd8tcelldependentzikaviruscontrolinthecnsamatteroftimeandnumbers |