Diverse pathogen-associated molecular patterns affect transcription of genes in the toll-like receptor signaling pathway in goat blood

Figures & data

Figure 1. Comparison of toll-like receptor signaling pathway gene expression in response to divers PAMPS compared to control. LPS: Escherichia coli-derived Lipopolysaccharide; PGN: Staphylococcus aureus-derived peptidoglycan; poly I:C, ODN 2216: CpG ODN (2216) class A, ODN 2006:CpG ODN (2006) class B, and control (phosphate buffered saline).

Table 1. Genes that were not expressed as a result of treatment with PBS (control).

Gene	Function
CCL2	Displays chemotactic activity for monocytes and basophils
CD80	Induces T-cell proliferation and cytokine production
CLEC4E	Recognizes damage-associated molecular patterns
HSPD1	Signaling molecule in the innate immune system
IFNG	A potent activator of macrophages
IRF1	Activator of genes involved in both innate and acquired immune responses
MAPK8	Involved in cellular processes such as proliferation, differentiation
NFKBIL1	Acts as negative regulator of Toll-like receptor
PTGS2	Associated with increased cell adhesion and phenotypic changes
UBE2V1	Involved in the control of differentiation by altering cell cycle behavior

Table 2. Fold change of up-regulated genes due to treatment with Poly I:C.

Gene	Fold change	Function
CHUK	250.9	Plays an essential role in the NF-kappa-B signaling pathway
FADD	29.4	An adaptor molecule that interacts with various cell surface receptors
HSPAIA	29.0	Maintains protein homeostasis during cellular stress
IFNA1	3.2	Stimulates the production protein kinase and an oligoadenylate synthetase
IFNB1	138.7	Has antiviral, antibacterial and anticancer activities
IRAK1	29.1	Plays a critical role in initiating innate immune response against foreign pathogens
IRF3	37.9	Plays a critical role in the innate immune response against DNA and RNA viruses
MAP3K1	27.4	Part of some signal transduction cascades, including the ERK and JNK kinase path
MAP3K4	69.8	Activates the CSBP2, P38 and JNK MAPK pathways
MYD88	29.1	Essential signal transducer in the interleukin-1 and TLR signaling pathways
PELI1	5.5	Involved in the TLR and IL-1 signaling pathways
PRKRA	6.0	Mediates the effects of interferon in response to viral infection
RELA	4.9	Initiates a vast array of stimuli related to many biological processes
ECSIT	14.6	Involved in the activation of NF-kappa-B via MAP3K1
TIRAP	81.2	Involved in TLR2 and TLR4 signaling pathways in the innate immune response
TLR3	28.5	Plays a fundamental role in pathogen recognition and activation
TLR6	8.7	Participates in the innate immune response to Gram-positive bacteria and fungi
TLR7	11.6	Key component of innate and adaptive immunity
TNF	2.3	Cytokine that mainly secreted by macrophages
TRAF6	30.3	Mediates signal transduction from, members of the TNF receptor superfamily
TICAM1	24.0	Mediates protein-protein interactions

Table 3. Fold change of down-regulated genes due to treatment with Poly I:C.

Gene	Fold change	Function
CD86	−11.8	Play a critical role in the early events of T-cell activation
IL10	−46.5	enhances B cell survival, proliferation, and antibody production
IL6	−27.5	Plays an essential role in the final differentiation of B-cells
LTA	−38.7	Mediates inflammatory, immunostimulatory, and antiviral responses
MAP3K7	−24.1	Controls transcription regulation and apoptosis
NFKB1	−40.4	Initiates a vast array of stimuli related to many biological processes
NFRKB	−45.2	Involved in transcriptional regulation
REL	−101.4	Regulate genes involved in apoptosis, inflammation and the immune response
RIPK2	−63.3	Plays an essential role in modulation of immune responses
TBK1	−17.6	Plays an essential role in regulating inflammatory responses to foreign agents
TLR1	−24.0	Plays an essential role in regulating inflammatory responses to foreign agents
TLR4	−13.3	Recognize pathogen-associated molecular patterns
TLR8	−3.4	Control host immune response against pathogens
TNFRSF1A	−89.5	Plays a role in cell survival, apoptosis, and inflammation
TOLLIP	−18.0	Regulates inflammatory signaling

Table 4. Fold change of up-regulated genes due to treatment with LPS.

Gene	Fold change	Function
BTK	112.39	Plays also a critical role in transcription regulation.
CD14	7.74	Mediates the innate immune response to bacterial lipopolysaccharide
CSF3	265.00	Cytokine that controls the production, differentiation, and function of granulocytes
CXCL10	19.00	Stimulation of monocytes, natural killer and T-cell migration
HMGB1	110.00	Plays a role in several cellular processes, including inflammation
HSPA1A	261.00	Maintains protein homeostasis during cellular
IL10	58.77	enhances B cell survival, proliferation, and antibody production
IRF3	6.54	Plays a critical role in the innate immune response against DNA and RNA viruses
LY86	144.15	Mediate the innate immune response to bacterial lipopolysaccharide
MAP3K1	190.82	Part of some signal transduction cascades
TAB1	25.77	Mediate various intracellular signaling pathways
MYD88	45.07	Essential signal transducer in the interleukin-1 and Toll-like receptor signaling pathways
PELI1	58.44	Involved in the TLR and IL-1 signaling pathways
PPARA	120.39	Involved in cell proliferation, cell differentiation
PRKRA	15.67	Mediates the effects of interferon in response to viral infection
RIPK2	37.06	Plays an essential role in modulation of innate and adaptive immune responses
SARM1	76.30	Involved in innate immune response
SIGIRR	19.73	Acts as a negative regulator of the Toll-like and IL-1R receptor signaling pathways
ECSIT	63.28	Adapter protein of the Toll-like and IL-1 receptor signaling pathway
TIRAP	2.73	Adapter involved in TLR2 and TLR4 signaling pathways in the innate immune response
TLR1	19.45	Plays a fundamental role in pathogen recognition and activation
TLR10	21.85	Recognize pathogen-associated molecular patterns
TLR3	42.37	Plays an essential role in regulating inflammatory responses to foreign agents
TLR4	133.58	Recognize pathogen-associated molecular patterns
TLR6	99.23	Participates in the innate immune response to Gram-positive bacteria and fungi
TLR8	43.27	Recognize pathogen-associated molecular patterns
TNF	8.42	Cytokine that mainly secreted by macrophages
TICAM1	83.11	Mediates protein-protein interactions

Table 5. Fold change of down-regulated genes due to treatment with LPS.

Gene	Fold change	Function
CSF2	−41.21	Controls the production, differentiation, and function macrophages
ELK1	−6.70	Binds to purine-rich DNA sequences
FADD	−54.57	Interacts with various cell surface receptors
IFNB1	−35.98	Has antiviral, antibacterial and anticancer activities
IL6	−2.44	Plays an essential role in the final differentiation of B-cells
IRAK1	−6.00	Plays a critical role in initiating innate immune response against pathogens
CD180	−74.88	Mediate the innate immune response to bacterial lipopolysaccharide
MAP3K7	−32.18	Controls cell functions including transcription regulation and apoptosis
NFKB1	−2.27	Initiates a vast array of stimuli related to many biological processes
NFRKB	−47.68	Involved in transcriptional regulation, DNA replication
RELA	−12.35	Initiates by a vast array of stimuli related to many biological processes
TBK1	−10.53	Plays an essential role in regulating inflammatory responses
TLR7	−34.56	Key component of innate and adaptive immunity
TNFRSF1A	−47.29	Plays a role in cell survival, apoptosis, and inflammation
TRAF6	−13.52	Associated with, and mediate signal transduction

Table 6. Fold change of up-regulated genes due to treatment with ODN 2006.

Gene	Fold change	Function
CD86	10.6	Play a critical role in the early events of T-cell activation
CHUK	9	Plays an essential role in the NF-kappa-B signaling pathway
CSF2	3.3	Cytokine that controls the production, differentiation
CSF3	2.7	Cytokine that controls the production
ELK1	46.8	Binds to purine-rich DNA sequences
HRAS	2.8	Involved in the activation of Ras protein signal transduction
HSPA1A	368.8	Maintains protein homeostasis during cellular stress
IFNB1	2.6	Has antiviral, antibacterial and anticancer activities
IKBKB	5.71	Plays an essential role in the NF-kappa-B signaling pathway
IRAK2	30.17	Essential regulators of IL-1R and TLR-mediated signaling
IRF3	251	Plays a critical role in the innate immune response
LTA	57.6	Mediates a large variety of inflammatory responses
MAP3K1	4.3	Part of some signal transduction cascades
TAB1	3.1	Mediate various intracellular signaling pathways
MAP4K4	3.8	Activates the CSBP2, P38 and JNK MAPK pathways
PELI1	18	Involved in the TLR and IL-1 signaling pathways
RELA	26.3	Initiates biological processes such as inflammation, immunity, differentiation
TBK1	3	Plays an essential role in regulating inflammatory responses to foreign agents
TIRAP	32.3	Adapter involved in TLR2 and TLR4 signaling pathways
TLR1	2.4	Plays a fundamental role in pathogen recognition
TLR3	4.3	Plays an essential role in regulating inflammatory responses to foreign agents
TLR9	15.19	Control host immune response against pathogens
TNF	15.8	Cytokine that mainly secreted by macrophages
TOLLIP	2.24	regulates inflammatory signaling
TRAF6	8.41	Associated with, and mediate signal transduction
TICAM1	8.8	Mediates protein-protein interactions

Table 7. Fold change of down-regulated genes due to treatment with ODN 2006.

Gene	Fold change	Function
CASP8	−662.8	Involved in the signaling pathways of apoptosis, necrosis and inflammation
CD14	−305.4	Mediates the innate immune response to bacterial lipopolysaccharide
IL10	−3.21	Enhances B cell survival, proliferation, and antibody production
IL1B	−98.00	Induces prostaglandin synthesis, neutrophil influx and activation
IL6	−14.6	Plays an essential role in the final differentiation of B-cells
JUN	−314.7	Involved in the signaling pathways of apoptosis, necrosis and inflammation
CD180	−65.4	Mediate the innate immune response to bacterial lipopolysaccharide
MAP2K4	−243.19	Act as an integration point for multiple biochemical signals
MAP3K7	−103.9	Controls a variety of cell functions including transcription regulation
MAPK8IP3	−536.8	Regulate the activity of numerous protein kinases
NFKB1	−321.23	Initiates a vast array of stimuli related to many biological processes
NFRKB	−16.4	Involved in transcriptional regulation, DNA replication
NR2C2	−54.0	Function in many biological processes
SIGIRR	−11.2	Acts as a negative regulator of the Toll-like pathway
TICAM2	−99.5	Regulate the MYD88-independent pathway
TLR10	−457.5	They recognize pathogen-associated molecular patterns
TLR2	−628.2	Plays a fundamental role in pathogen recognition
TNFRSF1A	−44.1	Plays a role in cell survival, apoptosis, and inflammation
UBE2N	−34.6	Control of progress through the cell cycle and differentiation

Table 8. Fold change of up-regulated genes due to treatment with ODN 2216.

Gene	Fold change	Function
CD86	1.8	Play a critical role in the early events of T-cell activation
CHUK	49.1	DNA damages or other cellular stresses
CSF2	21.9	Controls the production, differentiation, and function of macrophages
CSF3	561.6	Controls the production, differentiation, and function of granulocytes
ELK1	19.7	Binds to purine-rich DNA sequences
HSPA1A	659.3	Plays a pivotal role in the protein quality control system
IFNA1	73.5	Stimulates the production of two enzymes
IFNB1	33.4	Has antiviral, antibacterial and anticancer activities
IRAK1	118.4	Plays a critical role in initiating innate immune response
IRAK2	12.98	Participate in the IL1-induced upregulation of NF-kappaB
IRF3	8.7	Plays a critical role in the innate immune response against DNA and RNA viruses
LTA	24.3	Mediates a large variety of inflammatory responses
MAP3K1	28.23	Part of some signal transduction cascades
MAP4K4	12.8	Play a role in the response to environmental stress and cytokines
PELI1	13.19	Involved in the TLR and IL-1 signaling pathways
RELA	189.1	Involved in biological processes such as inflammation and immunity
SARM1	148.6	Involved in innate immune response
ECSIT	28.4	Adapter protein of the Toll-like and IL-1 receptor signaling pathway
TIRAP	12.18	Adapter involved in TLR2 and TLR4 signaling pathways
TLR1	7.57	Plays a fundamental role in pathogen recognition
TLR6	15.5	Participates in the innate immune response to Gram-positive bacteria and fungi
TLR9	7.7	They recognize pathogen-associated molecular patterns
TNF	5.8	Cytokine that mainly secreted by macrophages
TRAF6	56.7	Associated with, and mediate signal transduction
TICAM1	29.8	Mediates protein-protein interactions

Table 9. Fold change of down-regulated genes due to treatment with ODN 2216.

Gene	Fold change	Function
CD14	−127.8	Mediates the innate immune response to bacterial lipopolysaccharide
FADD	−6.6	An adaptor molecule that interacts with various cell surface receptors
HRAS	−57.2	Involved in the activation of Ras protein signal transduction
IL10	−14.4	Enhances B cell survival, proliferation, and antibody production
IL1B	−130.0	Involved in a variety of cellular activities
IL6	−18.3	Plays an essential role in the final differentiation of B-cells
CD180	−83.7	Mediate the innate immune response to bacterial lipopolysaccharide
TAB1	−102.3	Mediate various intracellular signaling pathways
MAPK8IP3	−2.3	Regulate the activity of numerous protein kinases of the JNK signaling pathway
NFKB1	−7.44	Initiates a vast array of stimuli related to many biological processes
NFKBIA	−201.1	Interacts with REL dimers to inhibit NF-kappa-B/REL complexes
NFRKB	−4.3	Involved in transcriptional regulation, DNA replication and probably DNA repair
REL	−190.4	Regulate genes involved in apoptosis and inflammation
SIGIRR	−31.6	Acts as a negative regulator of the toll-like receptor signaling pathway
TBK1	−1.4	Plays an essential role in regulating inflammatory responses to foreign agents
TLR3	−9.3	Plays an essential role in regulating inflammatory responses to foreign agents
TLR4	−3.2	Recognize pathogen-associated molecular patterns
TOLLIP	−1.6	Regulates inflammatory signaling
UBE2N	−50.77	Plays a role in the control of progress through the cell cycle and differentiation

Table 10. Fold change of up-regulated genes due to treatment with PGN.

Gene	Fold change	Function
CHUK	790.3	Plays an essential role in the NF-kappa-B signaling pathway
CSF2	1.58	Controls the production, differentiation
CSF3	130.53	Controls the production, differentiation, and function of granulocytes
CXCL10	25.5	Stimulation of monocytes, natural killer and T-cell migration
HSPA1A	37.2	Mediates the folding of newly translated proteins in the cytosol
IFNA1	312.2	Have antiviral activities
IKBKB	26.91	Plays an essential role in the NF-kappa-B signaling pathway
IRF3	158.72	Regulates the transcription of type I IFN genes
PPARA	39.4	Involved in cell proliferation, cell differentiation and in immune responses
PRKRA	48.3	Mediates the effects of interferon in response to viral infection
ECSIT	25.4	Adapter protein of the Toll-like and IL-1 receptor signaling pathway
TLR10	3.93	Participates in the innate immune response to microbial agents
TLR2	36.5	Participates in the innate immune response to Gram-positive bacteria and fungi
TLR8	4.4	Key component of innate and adaptive immunity
TNF	57.7	Induce cell death of certain tumor cell lines

Table 11. Fold change of down-regulated genes due to treatment with PGN.

PGN	Fold change	Function
CD14	−5.3	It cooperates with other proteins to mediate the innate immune
CD86	−2.6	Involved in the costimulatory signal essential for T-lymphocyte proliferation
ELK1	−4.0	Promoter of the c-fos proto-oncogene
HRAS	−1.4	Involved in the activation of Ras protein signal transduction
IL10	−13.0	Cytokine has pleiotropic effects in immunoregulation and inflammation
IRAK2	18.4	Participates in the IL1-induced upregulation of NF-kappaB
JUN	−3.0	Transcription factor that recognizes and binds to the enhancer heptamer motif
LTA	−2.8	Mediates inflammatory, immunostimulatory, and antiviral responses
LY86	−5.1	Cooperate with CD180 and TLR4 to mediate the innate immune response
MAP3K1	−3.2	Component of a protein kinase signal transduction cascade
MAP3K7	−1.0	Mediates the signaling transduction
TAB1	−6.1	Mediate various intracellular signaling pathways
MAP4K4	−20.3	Activates MAPK8/JNK pathway
NFKB2	−8.6	Function as both a transcriptional activator or repressor
PELI1	−22.8	Involved in the TLR and IL-1 signaling pathways
REL	−1.0	Regulate genes involved in apoptosis and inflammation
SIGIRR	−36.6	Regulator of the Toll-like and IL-1R receptor signaling pathways
TBK1	−2.9	Mediate NFKB activation in response to certain growth factors
TICAM2	−6.4	Functions as sorting adapter in LPS-TLR4
TIRAP	−26.9	Adaptor protein involved in the TLR4 signaling pathway of the immune system
TLR1	−2.3	Mediate the innate immune response to bacterial lipoproteins or lipopeptides
TLR3	−1.1	It recognizes dsRNA associated with viral infection
TLR5	−7.7	Recognizes bacterial flagellin
TNFRSF1A	−11.5	Receptor for TNFSF2/TNF-alpha
TOLLIP	−18.6	regulates inflammatory signaling
TRAF6	−10.1	Protein mediates signaling
TICAM1	−4.0	Mediates protein-protein interactions
UBE2N	−10.9	Important cellular mechanism for targeting proteins for degradation