PMID- 37275883
OWN - NLM
STAT- MEDLINE
DCOM- 20230613
LR  - 20231210
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 14
DP  - 2023
TI  - Single cell transcriptomics of bone marrow derived macrophages reveals Ccl5 as a 
      biomarker of direct IFNAR-independent responses to DNA sensing.
PG  - 1199730
LID - 10.3389/fimmu.2023.1199730 [doi]
LID - 1199730
AB  - INTRODUCTION: The type I interferon (IFN) response is an innate immune program 
      that mediates anti-viral, anti-cancer, auto-immune, auto-inflammatory, and 
      sterile injury responses. Bone marrow derived macrophages (BMDMs) are commonly 
      used to model macrophage type I IFN responses, but the use of bulk measurement 
      techniques obscures underlying cellular heterogeneity. This is particularly 
      important for the IFN response to immune stimulatory double-stranded DNA (dsDNA) 
      because it elicits overlapping direct and indirect responses, the latter of which 
      depend on type I IFN cytokines signaling via the IFN alpha receptor (IFNAR) to 
      upregulate expression of interferon stimulated genes (ISGs). Single cell 
      transcriptomics has emerged as a powerful tool for revealing functional 
      variability within cell populations. METHODS: Here, we use single cell RNA-Seq to 
      examine BMDM heterogeneity at steady state and after immune-stimulatory DNA 
      stimulation, with or without IFNAR-dependent amplification. RESULTS: We find that 
      many macrophages express ISGs after DNA stimulation. We also find that a subset 
      of macrophages express ISGs even if IFNAR is inhibited, suggesting that they are 
      direct responders. Analysis of this subset reveals Ccl5 to be an 
      IFNAR-independent marker gene of direct DNA sensing cells. DISCUSSION: Our 
      studies provide a method for studying direct responders to IFN-inducing stimuli 
      and demonstrate the importance of characterizing BMDM models of innate immune 
      responses with single cell resolution.
CI  - Copyright (c) 2023 McCarty, Yu, Ninh, Calcagno, Lee and King.
FAU - McCarty, Emily
AU  - McCarty E
AD  - Department of Bioengineering, Jacobs School of Engineering, University of 
      California San Diego, La Jolla, CA, United States.
FAU - Yu, Justin
AU  - Yu J
AD  - Department of Bioengineering, Jacobs School of Engineering, University of 
      California San Diego, La Jolla, CA, United States.
FAU - Ninh, Van K
AU  - Ninh VK
AD  - Department of Bioengineering, Jacobs School of Engineering, University of 
      California San Diego, La Jolla, CA, United States.
FAU - Calcagno, David M
AU  - Calcagno DM
AD  - Department of Bioengineering, Jacobs School of Engineering, University of 
      California San Diego, La Jolla, CA, United States.
FAU - Lee, Jodi
AU  - Lee J
AD  - Department of Bioengineering, Jacobs School of Engineering, University of 
      California San Diego, La Jolla, CA, United States.
FAU - King, Kevin R
AU  - King KR
AD  - Department of Bioengineering, Jacobs School of Engineering, University of 
      California San Diego, La Jolla, CA, United States.
AD  - Division of Cardiovascular Medicine, Department of Medicine, University of 
      California San Diego, La Jolla, CA, United States.
LA  - eng
GR  - DP2 AR075321/AR/NIAMS NIH HHS/United States
GR  - T32 HL007444/HL/NHLBI NIH HHS/United States
GR  - S10 OD026929/OD/NIH HHS/United States
GR  - R00 HL129168/HL/NHLBI NIH HHS/United States
GR  - T32 HL105373/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20230518
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Biomarkers)
RN  - 9007-49-2 (DNA)
RN  - 0 (Interferon Type I)
RN  - 0 (Interferon-alpha)
SB  - IM
MH  - Biomarkers
MH  - DNA
MH  - *Interferon Type I/metabolism
MH  - Interferon-alpha
MH  - Macrophages
MH  - *Transcriptome
MH  - Animals
MH  - Mice
PMC - PMC10232813
OTO - NOTNLM
OT  - Ccl5
OT  - Ifnar
OT  - Irf3
OT  - dsDNA
OT  - interferon stimulated genes
OT  - macrophages
OT  - single cell RNA-Seq
OT  - transcriptomics
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- 2023/06/05 19:10
MHDA- 2023/06/07 06:42
PMCR- 2023/01/01
CRDT- 2023/06/05 12:23
PHST- 2023/04/03 00:00 [received]
PHST- 2023/05/02 00:00 [accepted]
PHST- 2023/06/07 06:42 [medline]
PHST- 2023/06/05 19:10 [pubmed]
PHST- 2023/06/05 12:23 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2023.1199730 [doi]
PST - epublish
SO  - Front Immunol. 2023 May 18;14:1199730. doi: 10.3389/fimmu.2023.1199730. 
      eCollection 2023.