PMID- 36148245
OWN - NLM
STAT- MEDLINE
DCOM- 20220926
LR  - 20220927
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 13
DP  - 2022
TI  - TLR2-induced CD8(+) T-cell deactivation shapes dendritic cell differentiation in 
      the bone marrow during sepsis.
PG  - 945409
LID - 10.3389/fimmu.2022.945409 [doi]
LID - 945409
AB  - Sepsis is associated with profound immune dysregulation that increases the risk 
      for life-threatening secondary infections: Dendritic cells (DCs) undergo 
      functional reprogramming due to yet unknown changes during differentiation in the 
      bone marrow (BM). In parallel, lymphopenia and exhaustion of T lymphocytes 
      interfere with antigen-specific adaptive immunity. We hypothesized that there 
      exists a link between T cells and the modulation of DC differentiation in the BM 
      during murine polymicrobial sepsis. Sepsis was induced by cecal ligation and 
      puncture (CLP), a model for human bacterial sepsis. At different time points 
      after CLP, the BM and spleen were analyzed in terms of T-cell subpopulations, 
      activation, and Interferon (IFN)-gamma synthesis as well as the number of pre-DCs. 
      BM-derived DCs were generated in vitro. We observed that naive and virtual memory 
      CD8(+) T cells, but not CD4(+) T cells, were activated in an antigen-independent 
      manner and accumulated in the BM early after CLP, whereas lymphopenia was evident 
      in the spleen. The number of pre-DCs strongly declined during acute sepsis in the 
      BM and almost recovered by day 4 after CLP, which required the presence of CD8(+) 
      T cells. Adoptive transfer experiments and in vitro studies with purified T cells 
      revealed that Toll-like receptor 2 (TLR2) signaling in CD8(+) T cells suppressed 
      their capacity to secrete IFN-gamma and was sufficient to change the transcriptome of 
      the BM during sepsis. Moreover, the diminished IFN-gamma production of CD8(+) T cells 
      favored the differentiation of DCs with increased production of the 
      immune-activating cytokine Interleukin (IL)-12. These data identify a novel role 
      of CD8(+) T cells in the BM during sepsis as they sense TLR2 ligands and control 
      the number and function of de novo differentiating DCs.
CI  - Copyright (c) 2022 Antoni, Pylaeva, Budeus, Jablonska, Klein-Hitpass, Dudda and 
      Flohe.
FAU - Antoni, Anne-Charlotte
AU  - Antoni AC
AD  - Department of Trauma, Hand, and Reconstructive Surgery, University Hospital 
      Essen, University Duisburg-Essen, Essen, Germany.
FAU - Pylaeva, Ekaterina
AU  - Pylaeva E
AD  - Department of Otorhinolaryngology, University Hospital Essen, University 
      Duisburg-Essen, Essen, Germany.
FAU - Budeus, Bettina
AU  - Budeus B
AD  - Institute of Cell Biology, University Hospital Essen, University Duisburg-Essen, 
      Essen, Germany.
FAU - Jablonska, Jadwiga
AU  - Jablonska J
AD  - Department of Otorhinolaryngology, University Hospital Essen, University 
      Duisburg-Essen, Essen, Germany.
FAU - Klein-Hitpass, Ludger
AU  - Klein-Hitpass L
AD  - Institute of Cell Biology, University Hospital Essen, University Duisburg-Essen, 
      Essen, Germany.
FAU - Dudda, Marcel
AU  - Dudda M
AD  - Department of Trauma, Hand, and Reconstructive Surgery, University Hospital 
      Essen, University Duisburg-Essen, Essen, Germany.
FAU - Flohe, Stefanie B
AU  - Flohe SB
AD  - Department of Trauma, Hand, and Reconstructive Surgery, University Hospital 
      Essen, University Duisburg-Essen, Essen, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220906
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Antigens)
RN  - 0 (Cytokines)
RN  - 0 (TLR2 protein, human)
RN  - 0 (Tlr2 protein, mouse)
RN  - 0 (Toll-Like Receptor 2)
RN  - 187348-17-0 (Interleukin-12)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Antigens
MH  - Bone Marrow
MH  - CD8-Positive T-Lymphocytes
MH  - Cell Differentiation
MH  - Cytokines
MH  - Dendritic Cells
MH  - Humans
MH  - Interferon-gamma
MH  - Interleukin-12
MH  - *Lymphopenia
MH  - Mice
MH  - *Sepsis
MH  - Toll-Like Receptor 2
PMC - PMC9488929
OTO - NOTNLM
OT  - T cells
OT  - TLR - toll-like receptor
OT  - bone marrow
OT  - dendritic cells
OT  - differentiation
OT  - immunosuppression
OT  - sepsis
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/09/24 06:00
MHDA- 2022/09/28 06:00
PMCR- 2022/01/01
CRDT- 2022/09/23 02:56
PHST- 2022/05/16 00:00 [received]
PHST- 2022/07/15 00:00 [accepted]
PHST- 2022/09/23 02:56 [entrez]
PHST- 2022/09/24 06:00 [pubmed]
PHST- 2022/09/28 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2022.945409 [doi]
PST - epublish
SO  - Front Immunol. 2022 Sep 6;13:945409. doi: 10.3389/fimmu.2022.945409. eCollection 
      2022.