REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
anti-GFAP rabbit mAb	Roche	Cat#05269784001
Texas Red conjugated goat anti-rabbit IgG	Thermo Fisher Scientific	Cat# T-2767; RRID:AB_2556776
FITC anti-CD11b	eBioscience	Cat#11–0112–85; RRID: AB_464936
APC anti-CD45	eBioscience	Cat#17–0451–83; RRID:AB_469393
PerCP anti-Ly-6C	Biolegend	Cat#128028; RRID:AB_10897805
PE anti-mouse CD45R/B220	BD Biosciences	Cat#553089; RRID:AB_394619
PE anti-mouse TER-119	Biolegend	Cat#116207; RRID:AB_313708
PE anti-O4	R&D systems	Cat#FAB1326P; RRID:AB_664169
PE anti-CD105	eBioscience	Cat#12–1051–82; RRID:AB_657524
PE anti-CD140a	eBioscience	Cat#12–1401–81; RRID:AB_657615
PE anti-Ly-6G	Biolegend	Cat#127608; RRID:AB_2129141
BV421 anti-CD3,	BioLegend	Cat#100227; RRID:AB_10900227
BV605 anti-CD4	BioLegend	Cat#100547; RRID:AB_11125962
FITC anti-IFNγ	BioLegend	Cat#505806; RRID:AB_315400
PE anti-IL-17a	eBioscience	Cat#12–7177–81; RRID:AB_763582
APC anti-IL-10	BioLegend	Cat#505010; RRID:AB_315364
PerCP-Cy5.5 anti-FoxP3	eBioscience	Cat#45–5773–82; RRID:AB_914351
CD11b Microbead for mouse and human	Miltenyi	Cat#130–049–601
anti-Histone H3 rabbit polyclonal antibody	Sigma-Aldrich	Cat#07–690; RRID:AB_417398
anti-Lamin B1 rabbit mAb (HRP Conjugate)	Cell Signaling Technology	Cat#15068S; RRID:AB_2798695
anti-NF-κB p65 rabbit mAb	Cell Signaling Technology	Cat#8242S; RRID:AB_10859369
anti-Bsg rabbit mAb	Thermo Fisher Scientific	Cat#MA5–32534; RRID:AB_2809811
anti-Hk2 rabbit mAb	Cell signaling Technology	Cat#2867; RRID:AB_2232946
anti-p65 rabbit mAb	Cell Signaling Technology	Cat#8242; RRID:AB_10859369
control IgG isotype antibody	Cell Signaling Technology	Cat#3900S; RRID:AB_1550038
anti-MAVS rabbit mAb	Cell Signaling Technology	Cat#4983; RRID:AB_823566
anti-MAVS rabbit mAb	Cell Signaling Technology	Cat#24930S; RRID:AB_2798889
anti-MAVS mouse mAb	Santa Cruz Biotechnology	Cat#sc-365333; RRID:AB_10844335
anti-MAVS rabbit polyclonal Ab	abcam	Cat#ab189109
anti-cPLA2 (4–4B-3C) mouse mAb	Santa Cruze Biotechnology	Cat#sc-454; RRID:AB_627288
anti-cPLA2 rabbit mAb	Cell Signaling Technology	Cat#2832; RRID:AB_2164442
anti-HK2 rabbit mAb	abcam	Cat#ab228819
anti-HK2 rabbit mAb	Cell Signaling Technology	Cat#2867; RRID:AB_2232946
anti-HK2 (B8) mouse mAb	Santa Cruz Biotechnology	Cat#sc-374091; RRID:AB_10917915
anti-flag mouse mAb	Sigma-Aldrich	Cat#F1804; RRID:AB_262044
anti-flag rabbit polyclonal Ab	Sigma-Aldrich	Cat#F7425; RRID:AB_439687
anti-GFP rabbit polyclonal Ab	abcam	Cat#ab290; RRID:AB_303395
anti-rabbit IgG HRP-linked Ab	Cell Signaling Technology	Cat#7074S; RRID:AB_2099233
anti-mouse IgG HRP-linked Ab	Cell Signaling Technology	Cat#7076S; RRID:AB_330924
goat anti-rabbit IgG poly-HRP	Invitrogen	Cat#32260; RRID:AB_1965959
goat anti-mouse IgG poly-HRP	Invitrogen	Cat#32230; RRID:AB_1965958
anti-Tom20 rabbit polyclonal Ab	Santa Cruz Biotechnology	Cat#sc-11415; RRID:AB_2207533
AF635 conjugated anti-mouse IgG goat Ab	Life Technologies	Cat#A31574; RRID:AB_1500640
biotinylated anti-rabbit immunoglobulins goat Ab	Agilent/Dako	Cat#E0432; RRID:AB_2313609
Cy3 conjugated mouse anti-human GFAP	Sigma-Aldrich	Cat#C9205; RRID:AB_476889
anti-GFAP mouse mAb	Millipore	Cat#MAB360; RRID:AB_11212597
anti-COX4-I1 goat polyclonal Ab	R&D Systems	Cat#AF5814; RRID:AB_2085286
anti-NF-κB p65 (acetyl-Lys310) rabbit polyclonal Ab	Sigma-Aldrich	Cat#SAB4502616; RRID:AB_10745506
anti-mouse c3d goat polyclonal antibody	R&D Systems	Cat#AF2655; RRID:AB_2066622
AF488 conjugated anti-rabbit IgG goat Ab	Thermo Fisher Scientific	Cat#A11008; RRID:AB_143165
AF488 conjugated anti-goat IgG donkey antibody	Thermo Fisher Scientific	Cat#A11055; RRID:AB_2534102
AF647 anti-rabbit IgG donkey fab fragment	Jackson Immunoresearch	Cat#711–607–003; RRID:AB_2340626
AF647 conjugated anti-mouse IgG donkey Ab	abcam	Cat#ab150107
Rhodamine anti-mouse IgG donkey fab fragment	Jackson Immunoresearch	Cat#715–297–003; RRID:AB_2340836
AF405 conjugated anti-mouse IgG goat antibody	Thermo Fisher Scientific	Cat#A31553; RRID:AB_221604
AF405 conjugated anti-rabbit IgG goat antibody	Thermo Fisher Scientific	Cat#A31556; RRID:AB_221605
Bacterial and Virus Strains
Non-viable desiccated M.Tuberculosis H-37Ra	BD Bioscience	Cat#231141
NEB Stable E. Coli	New England Biolabs	Cat#C3040
NEB 10-beta Competent E. coli	New England Biolabs	Cat#C3019
Biological Samples
Human fetal astrocytes	Laboratory of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development	N/A
Human pathology samples	University of Montreal Health Centre	N/A
Paraffin-embedded brain sections	Neuropathology Department of the Notre Dame Hospital	N/A
Chemicals, Peptides, and Recombinant Proteins
MOG35–55 peptide	Genemed Synthesis	Cat#110582
Incomplete Freund’s adjuvant	BD Bioscience	Cat#263910
Miglustat hydrochloride	MedChemExpress	Cat#HY-17020A
Miglustat	BOC Sciences	Cat#72599–27–0
Pertussis toxin	List biological Laboratories	Cat#180
Papain	Sigma-Aldrich	Cat#P4762
Collagenase D	Roche	Cat#11088858001
DNase I	Thermo Fisher Scientific	Cat#90083
DNase I	QIAGEN	Cat#79254
Percoll	GE Healthcare	Cat#17–5445–01
UltraComp eBeads™ Compensation Beads	Invitrogen	Cat#01–2222–41
PMA (phorbol 12-myristate 13-acetate)	Sigma-Aldrich	Cat#P1585
Ionomycin	Sigma-Aldrich	Cat#I9657
GolgiSTOP	BD Biosciences	Cat#554724
Taqman Fast Universal PCR Master Mix	Life Technologies	Cat#4367846
Fast SYBR Green Master Mix	Thermo Fisher Scientific	Cat#4385612
Poly-L-Lysine	Sigma-Aldrich	Cat#P4707
Polybrene	Sigma-Aldrich	Cat#TR-1003-G
INTERFERin	Polyplus transfection	Cat#409
Mouse TNFα recombinant protein	R&D systems	Cat#410-MT-010
Human TNFα recombinant protein	R&D systems	Cat#210-TA-020
Mouse IFNγ recombinant protein	R&D systems	Cat#485-MI-100
Human IFNγ recombinant protein	R&D systems	Cat#285-IF-100
Accutase solution	Sigma-Aldrich	Cat#A6964
Pyrrophenone	Santa Cruz Biotechnology	Cat#sc-296161
N-acetyl cysteine	Sigma-Aldrich	Cat#A7250
HBEGF	Sigma-Aldrich	Cat#E4643
Rat II-1α recombinant protein	Sigma-Aldrich	Cat#I3901
Human TNFα recombinant protein	Cell Signaling Technology	Cat#8902SF
Human Complement Component C1q, Native Protein	MyBioSource	Cat#MBS143105
transferrin	Sigma-Aldrich	Cat#T-1147
BSA	Sigma-Aldrich	Cat#A8806
putrescine	Sigma-Aldrich	Cat#P5780
progesterone	Sigma-Aldrich	Cat#P8783
sodium selenite	Sigma-Aldrich	Cat#S5261
Formaldehyde solution, molecular grade	Sigma-Aldrich	Cat#F8775
Halt Protease and Phosphatase Inhibitor Cocktail	Thermo Fisher Scientific	Cat#78441
SuperSignal West Femto Maximum Sensitivity Substrate	Thermo Fisher Scientific	Cat#34095
KwikQuant Ultra Digital-ECL Substrate Solution	Kindle Biosciences	Cat#R1002
Protein A-Dynabeads magnetic beads	Thermo Fisher Scientific	Cat#10001D
Protein G-Dynabeads magnetic beads	Thermo Fisher Scientific	Cat#10003D
SeaKem GOLD agarose	Lonza	Cat#50152
Laminin	Sigma-Aldrich	Cat#L2020
MitoTracker™ Red CMXRos	Thermo Fisher Scientific	Cat#M7512
donkey serum	Sigma-Aldrich	Cat#D9663
goat serum	Sigma-Aldrich	Cat#G9023
mouse serum	Sigma-Aldrich	Cat#M5905
DAPI Fluoromount-G	SouthernBiotech	Cat#0100–20
NuPAGE LDS sample buffer	Invitrogen	Cat#NP0007
Hot Start Taq 2X Master Mix	New England Biolabs	Cat#M0496
FuGENE HD Transfection Reagent	Promega	Cat#E2311
UK-5099	Tocris Bioscience	Cat#4186
methylglyoxal solution	Sigma-Aldrich	Cat#M0252
Tyramide-AF488	Invitrogen	Cat#B40953
DAPI	Sigma-Aldrich	Cat#1.24653
Mowiol	Sigma-Aldrich	Cat#81381
OCT	Sakura	Cat#4583
2-DG	Sigma-Aldrich	Cat#D6134
Critical Commercial Assays
Intracellular antibody labeling kit	eBioscience	Cat#00–5523
Aqua LIVE/DEAD cell stain kit	Thermo Fisher Scientific	Cat#L34966
RNeasy Mini Kit	QIAGEN	Cat#74106
custom-made astrocyte-targeted nCounter Gene Expression code set	NanoString; (Rothhammer et al., 2017)	N/A
High-Capacity cDNA Reverse Transcription Kit	Life Technologies	Cat#4368813
ViraPower Packaging mix	Thermo Fisher Scientific	Cat#K497500
Lenti-X concentrator kit	Clontech	Cat#631231
CytoTox 96 Nonradioactive Cytotoxicity Assay kit	Promega	Cat#G1780
Cell Fractionation kit	Cell Signaling Technology	Cat#9038S
NucleoSpin® Gel and PCR Clean-up kit	Macherey-Nagel	Cat#740609.250
Mitochondria Isolation Kit	abcam	Cat#ab110170
Q5® Site-Directed Mutagenesis Kit	New England Biolabs	Cat#E0554S
Dual-Luciferase® Reporter Assay System	Promega	Cat#E1910
cellular reactive oxygen species detection assay kit	abcam	Cat#ab113851
CyQUANT cell proliferation assay kit	Invitrogen	Cat#C7026
L-lactate assay kit	Biomedical Research Service & Clinical Application	Cat#A-108
Pierce BCA Protein Assay Kit	Thermo Fisher Scientific	Cat#23225
Hexokinase Colorimetric Assay Kit	BioVision	Cat#K789
EnzyChrom Pyruvate Assay Kit	BioAssay Systems	Cat#EPYR-100
Seahorse XF Cell Mito Stress Test Kit	Agilent Technologies	Cat#103015–100
avidin-biotin blocking kit	Thermo Fisher Scientific	Cat#004303
Deposited Data
RNA-seq	This paper	GEO:GSE139531
Experimental Models: Cell Lines
Human: HEK-293FT	Invitrogen	Cat#R70007
Human: HEK-293	ATCC	Cat#CRL-1573
Mouse: N2A neuronal cells	ATCC	Cat#CCL-131
Experimental Models: Organisms/Strains
Mouse: C57BL/6J	The Jackson Laboratory	JAX: 000664
Mouse: NOD/ShiLtJ	The Jackson Laboratory	JAX: 001976
Mouse: B6;129-Mavstm1Zjc/J	The Jackson Laboratory	JAX: 008634
Oligonucleotides
See Table S1	This paper	N/A
Recombinant DNA
pLenti-Gfap-GFP-shB4galt6	This paper	N/A
pLenti-Gfap-GFP-shUgcg	This paper	N/A
pLenti-Gfap-GFP-shCers1	This paper	N/A
pLenti-Gfap-GFP-shCers2	This paper	N/A
pLenti-Gfap-GFP-shCers4	This paper	N/A
pLenti-Gfap-GFP-shCers5	This paper	N/A
pLenti-Gfap-GFP-shCers6	This paper	N/A
pLenti-Gfap-GFP-shPla2g4a	This paper	N/A
pLenti-Gfap-GFP-shMavs	This paper	N/A
pLenti-Gfap-GFP-shBsg	This paper	N/A
pCMV3-C-His-PLA2G4A	Sino Biological	Cat#MG51714-CH
pCMV3-C-His-PLA2G4A (S111P)	This paper	N/A
pCMV3-C-His-PLA2G4A (I399A/L400A/L552A)	This paper	N/A
pCMV3-C-His-PLA2G4A (R485H)	This paper	N/A
pCMV3-C-His-PLA2G4A (D549A)	This paper	N/A
pCMV3-C-His-PLA2G4A (S505A)	This paper	N/A
pCMV3-C-His-PLA2G4A (S505E)	This paper	N/A
pCMV3-C-His-PLA2G4A (dC2)	This paper	N/A
pCMV3-C-His-PLA2G4A (dPL)	This paper	N/A
pEGFP-PLA2G4A	(Casas et al., 2006)	N/A
pEGFP-PLA2G4A (D43N)	(Casas et al., 2006)	N/A
pEGFP-N1-C2	(Movahedi Naini et al., 2015)	N/A
pMP31–1 (flag-MAVS)	(Patel et al., 2012)	Addgene, Cat#45905; RRID:Addgene_45905
pMP31–1 (flag-MAVS, G67A/W68A/V69A)	This paper	N/A
pMP31–1 (flag-MAVS, W56A)	This paper	N/A
pcDNA3-flag-MAVS (M2–6L)	(Qi et al., 2017)	N/A
pcDNA3-flag-MAVS (M2)	(Qi et al., 2017)	N/A
pGL4.32(luc2P/NF-kB-RE/Hygro)	Promega	Cat#E8491
pRL Renilla luciferase	Promega	Cat#E2241
Software and Algorithms
R v3.3.3	The R Foundation	https://www.r-project.org/
DESeq2	(Love et al., 2014); RRID:SCR_015687	https://bioconductor.org/packages/release/bioc/html/DESeq2.html
GENE-E	Broad Institute	https://software.broadinstitute.org/GENE-E/
Ingenuity pathway analysis	QIAGEN; RRID:SCR_008653	http://www.ingenuity.com/products/pathways_analysis.html
Fiji	(Schindelin et al., 2012); RRID:SCR_002285	http://fiji.sc
Ensembl	(Yates et al., 2016); RRID:SCR_002344	http://www.ensembl.org/
JASPAR	(Sandelin et al., 2004); RRID:SCR_003030	http://jaspar.genereg.net
NEBaseChanger	New England Biolabs	http://nebasechanger.neb.com/
Primer3	(Untergasser et al., 2012); RRID:SCR_003139	http://bioinfo.ut.ee/primer3-0.4.0/
Primer-Blast	(Ye et al., 2012); RRID:SCR_003095	https://www.ncbi.nlm.nih.gov/tools/primer-blast/
TraceFinder 3.1 software	Thermo Fisher Scientific	N/A
Prism 8 software	GraphPad	N/A
Other