PMID- 34943787
OWN - NLM
STAT- MEDLINE
DCOM- 20220103
LR  - 20220103
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 10
IP  - 12
DP  - 2021 Nov 23
TI  - SARS-CoV-2 Spike Protein and Its Receptor Binding Domain Promote a 
      Proinflammatory Activation Profile on Human Dendritic Cells.
LID - 10.3390/cells10123279 [doi]
LID - 3279
AB  - Dendritic cells (DCs) are the most potent antigen-presenting cells, and their 
      function is essential to configure adaptative immunity and avoid excessive 
      inflammation. DCs are predicted to play a crucial role in the clinical evolution 
      of the infection by the severe acute respiratory syndrome (SARS) coronavirus 
      (CoV)-2. DCs interaction with the SARS-CoV-2 Spike protein, which mediates cell 
      receptor binding and subsequent fusion of the viral particle with host cell, is a 
      key step to induce effective immunity against this virus and in the S 
      protein-based vaccination protocols. Here we evaluated human DCs in response to 
      SARS-CoV-2 S protein, or to a fragment encompassing the receptor binding domain 
      (RBD) challenge. Both proteins increased the expression of maturation markers, 
      including MHC molecules and costimulatory receptors. DCs interaction with the 
      SARS-CoV-2 S protein promotes activation of key signaling molecules involved in 
      inflammation, including MAPK, AKT, STAT1, and NFkappaB, which correlates with the 
      expression and secretion of distinctive proinflammatory cytokines. Differences in 
      the expression of ACE2 along the differentiation of human monocytes to mature DCs 
      and inter-donor were found. Our results show that SARS-CoV-2 S protein promotes 
      inflammatory response and provides molecular links between individual variations 
      and the degree of response against this virus.
FAU - Barreda, Dante
AU  - Barreda D
AD  - Department of Immunology and Oncology, Spanish National Centre for Biotechnology, 
      28049 Madrid, Spain.
FAU - Santiago, Cesar
AU  - Santiago C
AD  - Department of Macromolecular Structures, Spanish National Centre for 
      Biotechnology, 28049 Madrid, Spain.
FAU - Rodriguez, Juan R
AU  - Rodriguez JR
AD  - Department of Molecular and Cell Biology, Spanish National Centre for 
      Biotechnology, 28049 Madrid, Spain.
FAU - Rodriguez, Jose F
AU  - Rodriguez JF
AD  - Department of Molecular and Cell Biology, Spanish National Centre for 
      Biotechnology, 28049 Madrid, Spain.
FAU - Casasnovas, Jose M
AU  - Casasnovas JM
AUID- ORCID: 0000-0002-2873-6410
AD  - Department of Macromolecular Structures, Spanish National Centre for 
      Biotechnology, 28049 Madrid, Spain.
FAU - Merida, Isabel
AU  - Merida I
AUID- ORCID: 0000-0003-2762-6241
AD  - Department of Immunology and Oncology, Spanish National Centre for Biotechnology, 
      28049 Madrid, Spain.
FAU - Avila-Flores, Antonia
AU  - Avila-Flores A
AUID- ORCID: 0000-0001-6278-2472
AD  - Department of Immunology and Oncology, Spanish National Centre for Biotechnology, 
      28049 Madrid, Spain.
LA  - eng
GR  - MINECO PID2019-108357RB-I00/10.13039/501100011033/Ministry of Economy, Industry 
      and Competitiveness/
GR  - CSIC-COVID19-032/Spanish National Research Council/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211123
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Cytokines)
RN  - 0 (DC-specific ICAM-3 grabbing nonintegrin)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Virus)
RN  - 0 (STAT Transcription Factors)
RN  - 0 (Spike Glycoprotein, Coronavirus)
RN  - 0 (spike protein, SARS-CoV-2)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 3.4.17.23 (ACE2 protein, human)
RN  - EC 3.4.17.23 (Angiotensin-Converting Enzyme 2)
SB  - IM
MH  - Angiotensin-Converting Enzyme 2/metabolism
MH  - Cell Adhesion Molecules/metabolism
MH  - Cell Differentiation
MH  - Cytokines/biosynthesis
MH  - Dendritic Cells/*pathology/*virology
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Humans
MH  - Inflammation/pathology
MH  - Lectins, C-Type/metabolism
MH  - Protein Domains
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Receptors, Cell Surface/metabolism
MH  - Receptors, Virus/*metabolism
MH  - SARS-CoV-2/*metabolism
MH  - STAT Transcription Factors/metabolism
MH  - Signal Transduction
MH  - Spike Glycoprotein, Coronavirus/*chemistry/*metabolism
MH  - Tissue Donors
PMC - PMC8699033
OTO - NOTNLM
OT  - ACE-2
OT  - COVID-19
OT  - cytokines
OT  - inflammation
COIS- The authors declare no conflict of interest.
EDAT- 2021/12/25 06:00
MHDA- 2022/01/04 06:00
PMCR- 2021/11/23
CRDT- 2021/12/24 01:03
PHST- 2021/10/11 00:00 [received]
PHST- 2021/11/10 00:00 [revised]
PHST- 2021/11/12 00:00 [accepted]
PHST- 2021/12/24 01:03 [entrez]
PHST- 2021/12/25 06:00 [pubmed]
PHST- 2022/01/04 06:00 [medline]
PHST- 2021/11/23 00:00 [pmc-release]
AID - cells10123279 [pii]
AID - cells-10-03279 [pii]
AID - 10.3390/cells10123279 [doi]
PST - epublish
SO  - Cells. 2021 Nov 23;10(12):3279. doi: 10.3390/cells10123279.