PMID- 32922405
OWN - NLM
STAT- MEDLINE
DCOM- 20210520
LR  - 20230721
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 11
DP  - 2020
TI  - CR4 Signaling Contributes to a DC-Driven Enhanced Immune Response Against 
      Complement-Opsonized HIV-1.
PG  - 2010
LID - 10.3389/fimmu.2020.02010 [doi]
LID - 2010
AB  - Dendritic cells (DCs) possess intrinsic cellular defense mechanisms to 
      specifically inhibit HIV-1 replication. In turn, HIV-1 has evolved strategies to 
      evade innate immune sensing by DCs resulting in suboptimal maturation and poor 
      antiviral immune responses. We previously showed that complement-opsonized HIV-1 
      (HIV-C) was able to efficiently infect various DC subsets significantly higher 
      than non-opsonized HIV-1 (HIV) and therefore also mediate a higher antiviral 
      immunity. Thus, complement coating of HIV-1 might play a role with respect to 
      viral control occurring early during infection via modulation of DCs. To 
      determine in detail which complement receptors (CRs) expressed on DCs was 
      responsible for infection and superior pro-inflammatory and antiviral effects, we 
      generated stable deletion mutants for the alpha-chains of CR3, CD11b, and CR4, CD11c 
      using CRISPR/Cas9 in THP1-derived DCs. We found that CD11c deletion resulted in 
      impaired DC infection as well as antiviral and pro-inflammatory immunity upon 
      exposure to complement-coated HIV-1. In contrast, sole expression of CD11b on DCs 
      shifted the cells to an anti-inflammatory, regulatory DC type. We here 
      illustrated that CR4 comprised of CD11c and CD18 is the major player with respect 
      to DC infection associated with a potent early pro-inflammatory immune response. 
      A more detailed characterization of CR3 and CR4 functions using our powerful tool 
      might open novel avenues for early therapeutic intervention during HIV-1 
      infection.
CI  - Copyright (c) 2020 Bermejo-Jambrina, Blatzer, Jauregui-Onieva, Yordanov, Hortnagl, 
      Valovka, Huber, Wilflingseder and Posch.
FAU - Bermejo-Jambrina, Marta
AU  - Bermejo-Jambrina M
AD  - Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, 
      Innsbruck, Austria.
AD  - Department of Experimental Immunology, Amsterdam Infection and Immunity 
      Institute, Academic Medical Center, University of Amsterdam, Amsterdam, 
      Netherlands.
FAU - Blatzer, Michael
AU  - Blatzer M
AD  - Experimental Neuropathology Unit, Infection and Epidemiology Department, 
      Institute Pasteur, Paris, France.
FAU - Jauregui-Onieva, Paula
AU  - Jauregui-Onieva P
AD  - Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, 
      Innsbruck, Austria.
FAU - Yordanov, Teodor E
AU  - Yordanov TE
AD  - Institute of Cell Biology, Biocenter, Medical University of Innsbruck, Innsbruck, 
      Austria.
FAU - Hortnagl, Paul
AU  - Hortnagl P
AD  - Central Institute for Blood Transfusion and Immunological Department, Innsbruck, 
      Austria.
FAU - Valovka, Taras
AU  - Valovka T
AD  - Institute of Cell Biology, Biocenter, Medical University of Innsbruck, Innsbruck, 
      Austria.
AD  - Department of Pediatrics I, Medical University of Innsbruck, Innsbruck, Austria.
FAU - Huber, Lukas A
AU  - Huber LA
AD  - Institute of Cell Biology, Biocenter, Medical University of Innsbruck, Innsbruck, 
      Austria.
FAU - Wilflingseder, Doris
AU  - Wilflingseder D
AD  - Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, 
      Innsbruck, Austria.
FAU - Posch, Wilfried
AU  - Posch W
AD  - Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, 
      Innsbruck, Austria.
LA  - eng
GR  - P 33510/FWF_/Austrian Science Fund FWF/Austria
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200814
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (CD11b Antigen)
RN  - 0 (CD11c Antigen)
RN  - 0 (CD18 Antigens)
RN  - 0 (Integrin alphaXbeta2)
RN  - 0 (Macrophage-1 Antigen)
RN  - 9007-36-7 (Complement System Proteins)
SB  - IM
MH  - CD11b Antigen/genetics
MH  - CD11c Antigen/genetics
MH  - CD18 Antigens/genetics
MH  - CRISPR-Cas Systems
MH  - Complement System Proteins/metabolism
MH  - Dendritic Cells/*immunology
MH  - HIV Infections/*immunology
MH  - HIV-1/*physiology
MH  - Humans
MH  - Immunity
MH  - Integrin alphaXbeta2/genetics/*metabolism
MH  - Macrophage-1 Antigen/genetics/*metabolism
MH  - Sequence Deletion/genetics
MH  - Signal Transduction
MH  - THP-1 Cells
PMC - PMC7457048
OTO - NOTNLM
OT  - CD11b
OT  - CD11c
OT  - HIV-1
OT  - complement
OT  - dendritic cell
EDAT- 2020/09/15 06:00
MHDA- 2021/05/21 06:00
PMCR- 2020/01/01
CRDT- 2020/09/14 05:50
PHST- 2020/05/15 00:00 [received]
PHST- 2020/07/24 00:00 [accepted]
PHST- 2020/09/14 05:50 [entrez]
PHST- 2020/09/15 06:00 [pubmed]
PHST- 2021/05/21 06:00 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2020.02010 [doi]
PST - epublish
SO  - Front Immunol. 2020 Aug 14;11:2010. doi: 10.3389/fimmu.2020.02010. eCollection 
      2020.