PMID- 35249041
OWN - NLM
STAT- MEDLINE
DCOM- 20220908
LR  - 20220924
IS  - 1662-8128 (Electronic)
IS  - 1662-811X (Print)
IS  - 1662-811X (Linking)
VI  - 14
IP  - 5
DP  - 2022
TI  - Streptococcus pneumoniae Impairs Maturation of Human Dendritic Cells and 
      Consequent Activation of CD4+ T Cells via Pneumolysin.
PG  - 569-580
LID - 10.1159/000522339 [doi]
AB  - Influenza A Virus (IAV), Staphylococcus aureus (staphylococci), and Streptococcus 
      pneumoniae (pneumococci) are leading viral and bacterial causes of pneumonia. 
      Dendritic cells (DCs) are present in the lower respiratory tract. They are 
      characterized by low expression of co-stimulatory molecules, including CD80 and 
      CD86 and high capacity of antigen uptake. Subsequently, DCs upregulate 
      co-stimulatory signals and cytokine secretion to effectively induce T-cell 
      priming. Here, we investigated these processes in response to bacterial and viral 
      single as well as coinfections using human monocyte-derived (mo)DCs. Irrespective 
      of single or coinfections, moDCs matured in response to IAV and/or staphylococcal 
      infections, secreted a wide range of cytokines, and activated CD4+, CD8+ as well 
      as double-negative T cells. In contrast, pneumococcal single and coinfections 
      impaired moDC maturation, which was characterized by low expression of CD80 and 
      CD86, downregulated expression of CD40, and a mild cytokine release resulting in 
      abrogated CD4+ T-cell activation. These actions were attributed to the 
      cholesterol-dependent cytotoxin pneumolysin (Ply). Infections with a 
      ply-deficient mutant resulted in restored moDC maturation and exclusive CD4+ 
      T-cell activation. These findings show that Ply has important immunomodulatory 
      functions, supporting further investigations in specific modalities of Ply-DC 
      interplay.
CI  - (c) 2022 The Author(s). Published by S. Karger AG, Basel.
FAU - Paulikat, Antje D
AU  - Paulikat AD
AD  - Department of Molecular Genetics and Infection Biology, University of Greifswald, 
      Greifswald, Germany.
FAU - Tolken, Lea A
AU  - Tolken LA
AD  - Department of Molecular Genetics and Infection Biology, University of Greifswald, 
      Greifswald, Germany.
FAU - Jachmann, Lana H
AU  - Jachmann LH
AD  - Department of Molecular Genetics and Infection Biology, University of Greifswald, 
      Greifswald, Germany.
FAU - Burchhardt, Gerhard
AU  - Burchhardt G
AD  - Department of Molecular Genetics and Infection Biology, University of Greifswald, 
      Greifswald, Germany.
FAU - Hammerschmidt, Sven
AU  - Hammerschmidt S
AD  - Department of Molecular Genetics and Infection Biology, University of Greifswald, 
      Greifswald, Germany.
FAU - Siemens, Nikolai
AU  - Siemens N
AD  - Department of Molecular Genetics and Infection Biology, University of Greifswald, 
      Greifswald, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220304
PL  - Switzerland
TA  - J Innate Immun
JT  - Journal of innate immunity
JID - 101469471
RN  - 0 (Bacterial Proteins)
RN  - 0 (Cytokines)
RN  - 0 (Streptolysins)
RN  - 0 (plY protein, Streptococcus pneumoniae)
SB  - IM
MH  - Bacterial Proteins
MH  - CD4-Positive T-Lymphocytes
MH  - *Coinfection/metabolism
MH  - Cytokines/metabolism
MH  - Dendritic Cells
MH  - Humans
MH  - *Influenza A virus
MH  - Streptococcus pneumoniae
MH  - Streptolysins
PMC - PMC9485967
OTO - NOTNLM
OT  - Dendritic cells
OT  - Influenza A virus
OT  - Pneumolysin
OT  - Staphylococcus aureus
OT  - Streptococcus pneumoniae
COIS- The authors have no conflicts of interest to declare.
EDAT- 2022/03/07 06:00
MHDA- 2022/09/09 06:00
PMCR- 2022/03/04
CRDT- 2022/03/06 20:37
PHST- 2021/12/02 00:00 [received]
PHST- 2022/01/25 00:00 [accepted]
PHST- 2022/03/07 06:00 [pubmed]
PHST- 2022/09/09 06:00 [medline]
PHST- 2022/03/06 20:37 [entrez]
PHST- 2022/03/04 00:00 [pmc-release]
AID - 000522339 [pii]
AID - jin-0014-0569 [pii]
AID - 10.1159/000522339 [doi]
PST - ppublish
SO  - J Innate Immun. 2022;14(5):569-580. doi: 10.1159/000522339. Epub 2022 Mar 4.