* Mouse only TRAF6 TRAF6 TRAF6 Endocytosed TLR4 TLR7/8 TLR13 TLR9 ssRNA Unmethylated CpG DNA Unmethylated CpG DNA dsRNA TLR3 TRIF TRIF TRAM RIP1 RIP1 23s rRNA TIRAP Profilin TLR12 Homodimer TLR11/12 Heterodimer TRAF3 TRAF3 TRAF3 IKK ε TBK-1 Proteasomal Degradation Ubiquitin Ubiquitin RICK/RIP2 RICK/RIP2 Procaspase-1 Procaspase-1 Caspase-1 Pro IL-1 β Pro IL-18 IL-1 β IL-18 Inflammation Pyroptosis NLRP3 TXNIP TXNIP Active State TRX TRX TXNIP TRX ROS Cathepsins Crystalline Structures Pannexin-1 P2X7 PAMPs NOX Enzymes NOD1 NOD2 Ubiquitin IKK β IKK β NF- κB NF- κB NF- κB NF- κB Activation MAPK Activation NF- κB NF- κB NF- κB IKK α IKK β IKK γ/NEMO IKK α IKK α AP-1 Activation TBK1 TBK1 pol III Viral DNA Viral RNA STING Intracellular Bacteria Proinflammatory Factors Cyclic Dinucleotides NEMO IRAK1 IRAK2 IRAK4 LPS TIRAP MyD88 MyD88 MyD88 ? Lipopeptides Flagella TLR5 TLR10 TLR2 TLR2 TLR1/6 CD14 CD14 TLR4/MD2 TRAF6 IRAK1 IRAK2 IRAK4 IRAK1 IRAK2 IRAK4 TAB2/3 TAB2/3 Muramyl Dipeptide Endocytosed Bacteria DAMPs Pore-forming toxins Calcium Influx? γ -D-glutamyl-meso diaminopimelic acid TAK1 TAK1 TAB1 TAB1 TAB2/3 IRF7 ASC AIM2 ASC Foreign dsDNA JAK1 JAK1 Tyk2 Tyk2 STAT1 STAT2 TRF9 ISGF3 IFN Stimulated Genes Type 1 IFNs IFNAR1 IFNAR2 MAVS Aggregation Dimerization TRIM25 Riplet RNF135 K63 Polyubiquitination Heterotetramer Formation RIG- I IRF7 Type 1 IFNs IRF3 IRF3 IRF3 IL-15 RANTES CXCL10 IL-1 β IL-6 IL-10 IL-16 iNOS TNF- α GM-CSF MIP-1 α MIP-1 β MCP-1 RANTES TAK1 TAB1 c-Jun JNK p50 p60 RelA c-Fas AP-1 AP-1 AP-1 CREB RAS Dectin-1 DC-SIGN Dectin-2 Mincle β -glycan SYK Fc γ R Fc γ R α -Mannose, Cord Factor High Mannose, α -Mannans High Mannose, Fucose SYK SYK RAF-1 NLRP3 Activation CARD9 ROS MALT1 Bcl-10 ptd Ins (3, 4, 5) P3 ptd Ins (4, 5) P2 PKC BTK RAC DAG RHO p38 PKC InsP 3 PLC γ PLC γ PI3K SYK Lyn Antigen ITAM IgG Antibodies Fc γ Rs α subunit γ 2 subunit SOS RAS CGAS Mda5 IPS-1 ERK JNK ADCC Phagocytosis Cytokine Release Oxidative Burst Ca 2+ Ca 2+ Export Calcineurin NFAT NFAT CREB p38/MAPK Parasites Bacteria Bacteria Fungi Bacteria Viruses Viruses Nucleus Inflammasome Formation Lysosome Mitochondria Endoplasmic Reticulum ©BioLegend, Inc. 2016 Innate Immune Signaling biolegend.com Endosomes Toll - Like Receptor Ligands TLR1 - Triacetylated lipopeptides TLR2 - Glycolipids, lipopeptides, lipoproteins TLR3 - Double-stranded RNA TLR4 - Lipopolysaccharide, heat shock proteins, fibrinogen TLR5 - Flagellin TLR6 - Diacyl lipopeptides TLR7 - Single-stranded RNA TLR8 - Single-stranded RNA (Human) Imidazoquinoline, poly T oligonucleotides (Mouse) TLR9 - Unmethylated CpG DNA, haemozoin TLR10 - ? TLR11* - Flagellin, profilin TLR12* - Profilin TLR13* - 23s rRNA Contact BioLegend US & Canada Toll-Free: 1.877.246.5343 (877-BIOLEGEND) International: 1.858.768.5800 Fax: 1.877.455.9587 email: [email protected], [email protected] 04-0069-00 US Headquarters: San Diego, CA 92121 Interactive Poster: biolegend.com/innate_signaling_poster We would like to thank Dr. Glen N. Barber of the University of Miami Miller School of Medicine for his contributions to this poster.