Cargando…

Rotavirus-Induced Expansion of Antigen-Specific CD8 T Cells Does Not Require Signaling via TLR3, MyD88 or the Type I Interferon Receptor

Rotavirus (RV) infection induces strong adaptive immunity. While protection from reinfection requires humoral immunity, initial clearance of infection depends on cytotoxic CD8 T cells. Type I classical dendritic cells (cDC1) excel at CD8 T cell induction through cross-presentation and are essential...

Descripción completa

Detalles Bibliográficos
Autores principales: Muleta, Konjit Getachew, Ulmert, Isabel, Hamza, Kedir Hussen, van Dijl, Sharné, Nakawesi, Joy, Lahl, Katharina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9022177/
https://www.ncbi.nlm.nih.gov/pubmed/35464475
http://dx.doi.org/10.3389/fimmu.2022.814491
_version_ 1784690024633073664
author Muleta, Konjit Getachew
Ulmert, Isabel
Hamza, Kedir Hussen
van Dijl, Sharné
Nakawesi, Joy
Lahl, Katharina
author_facet Muleta, Konjit Getachew
Ulmert, Isabel
Hamza, Kedir Hussen
van Dijl, Sharné
Nakawesi, Joy
Lahl, Katharina
author_sort Muleta, Konjit Getachew
collection PubMed
description Rotavirus (RV) infection induces strong adaptive immunity. While protection from reinfection requires humoral immunity, initial clearance of infection depends on cytotoxic CD8 T cells. Type I classical dendritic cells (cDC1) excel at CD8 T cell induction through cross-presentation and are essential for optimal cytotoxicity towards RV. Upon sensing of infection-induced innate immune signals through pattern recognition receptors (PRRs), cumulating in autocrine type I interferon (IFN) signaling, cDC1 mature and migrate to the draining lymph nodes (LNs), where they prime adaptive immune cells. To analyze which PRR pathways lead to robust cytotoxicity in the context of RV infection, we measured RV-specific CD8 T cell priming in mice deficient for Toll-like receptor 3 (TLR3), recognizing double-stranded RNA, or for MyD88, the adapter for all other TLRs and IL-1 family cytokines. Individual TLR3- and MyD88-mediated signaling was not required for the priming of CD8 T cell responses to RV and neither deficiency impacted on RV clearance. Surprisingly, the accumulation of RV-specific CD8 T cells was also not altered in the absence of type I IFN signaling, while their ability to produce IFNγ and granzyme were blunted. Together, this suggests a substantial level of redundancy in the sensing of RV infection and the translation of signals into protective CD8 T cell immunity.
format Online
Article
Text
id pubmed-9022177
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-90221772022-04-22 Rotavirus-Induced Expansion of Antigen-Specific CD8 T Cells Does Not Require Signaling via TLR3, MyD88 or the Type I Interferon Receptor Muleta, Konjit Getachew Ulmert, Isabel Hamza, Kedir Hussen van Dijl, Sharné Nakawesi, Joy Lahl, Katharina Front Immunol Immunology Rotavirus (RV) infection induces strong adaptive immunity. While protection from reinfection requires humoral immunity, initial clearance of infection depends on cytotoxic CD8 T cells. Type I classical dendritic cells (cDC1) excel at CD8 T cell induction through cross-presentation and are essential for optimal cytotoxicity towards RV. Upon sensing of infection-induced innate immune signals through pattern recognition receptors (PRRs), cumulating in autocrine type I interferon (IFN) signaling, cDC1 mature and migrate to the draining lymph nodes (LNs), where they prime adaptive immune cells. To analyze which PRR pathways lead to robust cytotoxicity in the context of RV infection, we measured RV-specific CD8 T cell priming in mice deficient for Toll-like receptor 3 (TLR3), recognizing double-stranded RNA, or for MyD88, the adapter for all other TLRs and IL-1 family cytokines. Individual TLR3- and MyD88-mediated signaling was not required for the priming of CD8 T cell responses to RV and neither deficiency impacted on RV clearance. Surprisingly, the accumulation of RV-specific CD8 T cells was also not altered in the absence of type I IFN signaling, while their ability to produce IFNγ and granzyme were blunted. Together, this suggests a substantial level of redundancy in the sensing of RV infection and the translation of signals into protective CD8 T cell immunity. Frontiers Media S.A. 2022-04-07 /pmc/articles/PMC9022177/ /pubmed/35464475 http://dx.doi.org/10.3389/fimmu.2022.814491 Text en Copyright © 2022 Muleta, Ulmert, Hamza, van Dijl, Nakawesi and Lahl 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 Immunology
Muleta, Konjit Getachew
Ulmert, Isabel
Hamza, Kedir Hussen
van Dijl, Sharné
Nakawesi, Joy
Lahl, Katharina
Rotavirus-Induced Expansion of Antigen-Specific CD8 T Cells Does Not Require Signaling via TLR3, MyD88 or the Type I Interferon Receptor
title Rotavirus-Induced Expansion of Antigen-Specific CD8 T Cells Does Not Require Signaling via TLR3, MyD88 or the Type I Interferon Receptor
title_full Rotavirus-Induced Expansion of Antigen-Specific CD8 T Cells Does Not Require Signaling via TLR3, MyD88 or the Type I Interferon Receptor
title_fullStr Rotavirus-Induced Expansion of Antigen-Specific CD8 T Cells Does Not Require Signaling via TLR3, MyD88 or the Type I Interferon Receptor
title_full_unstemmed Rotavirus-Induced Expansion of Antigen-Specific CD8 T Cells Does Not Require Signaling via TLR3, MyD88 or the Type I Interferon Receptor
title_short Rotavirus-Induced Expansion of Antigen-Specific CD8 T Cells Does Not Require Signaling via TLR3, MyD88 or the Type I Interferon Receptor
title_sort rotavirus-induced expansion of antigen-specific cd8 t cells does not require signaling via tlr3, myd88 or the type i interferon receptor
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9022177/
https://www.ncbi.nlm.nih.gov/pubmed/35464475
http://dx.doi.org/10.3389/fimmu.2022.814491
work_keys_str_mv AT muletakonjitgetachew rotavirusinducedexpansionofantigenspecificcd8tcellsdoesnotrequiresignalingviatlr3myd88orthetypeiinterferonreceptor
AT ulmertisabel rotavirusinducedexpansionofantigenspecificcd8tcellsdoesnotrequiresignalingviatlr3myd88orthetypeiinterferonreceptor
AT hamzakedirhussen rotavirusinducedexpansionofantigenspecificcd8tcellsdoesnotrequiresignalingviatlr3myd88orthetypeiinterferonreceptor
AT vandijlsharne rotavirusinducedexpansionofantigenspecificcd8tcellsdoesnotrequiresignalingviatlr3myd88orthetypeiinterferonreceptor
AT nakawesijoy rotavirusinducedexpansionofantigenspecificcd8tcellsdoesnotrequiresignalingviatlr3myd88orthetypeiinterferonreceptor
AT lahlkatharina rotavirusinducedexpansionofantigenspecificcd8tcellsdoesnotrequiresignalingviatlr3myd88orthetypeiinterferonreceptor