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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 LU ; Ulmert, Isabel LU ; Hamza, Kedir Hussen LU ; van Dijl, Sharné LU ; Nakawesi, Joy LU and Lahl, Katharina LU (2022) In Frontiers in Immunology 13.
Abstract

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... (More)

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.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
CD8 T cells, dendritic cells, innate immunity, pattern (re)cognition, rotavirus, type I IFN
in
Frontiers in Immunology
volume
13
article number
814491
publisher
Frontiers Media S. A.
external identifiers
  • scopus:85128625283
  • pmid:35464475
ISSN
1664-3224
DOI
10.3389/fimmu.2022.814491
language
English
LU publication?
yes
id
52bd15a0-f572-4fb0-a0f2-e05e2a36c64b
date added to LUP
2022-07-01 14:10:32
date last changed
2024-06-13 17:54:51
@article{52bd15a0-f572-4fb0-a0f2-e05e2a36c64b,
  abstract     = {{<p>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.</p>}},
  author       = {{Muleta, Konjit Getachew and Ulmert, Isabel and Hamza, Kedir Hussen and van Dijl, Sharné and Nakawesi, Joy and Lahl, Katharina}},
  issn         = {{1664-3224}},
  keywords     = {{CD8 T cells; dendritic cells; innate immunity; pattern (re)cognition; rotavirus; type I IFN}},
  language     = {{eng}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Immunology}},
  title        = {{Rotavirus-Induced Expansion of Antigen-Specific CD8 T Cells Does Not Require Signaling via TLR3, MyD88 or the Type I Interferon Receptor}},
  url          = {{http://dx.doi.org/10.3389/fimmu.2022.814491}},
  doi          = {{10.3389/fimmu.2022.814491}},
  volume       = {{13}},
  year         = {{2022}},
}