Table 2. Ingenuity iReport analysis of inflammasome-related datasets in THP-1 macrophages infected by T. cruzi for 3 h or 18 h (± ATP).
Pathways | Gene name | FoCus mols | P value |
T. cruzi infection of THP-1 mφs vs control (3h) | |||
Top biological and molecular functions | |||
1) Inflammatory responses/infection | ↓B2M, ↓BCL2, ↑CCL2, ↑CCL5, ↓CIITA, ↑CXCL1, ↑CXCL2, ↑NFKB1, ↑NFKB1A, ↓PYCARD, ↑RIPK2,↑TNF, ↓TXNIP | 13 | 5.91E-12–2.49E-04 |
1a. Recruitment of neutrophils/phagoCytes | ↑CCL2, ↑CCL5, ↑CXCL1, ↑CXCL2, ↓PYCARD, ↑RIPK2, ↑TNF | 7 | 2.77E-10 |
1b. Activation of leukoCyte/lymphoCytes | ↓BCL2, ↑CCL2, ↑CCL5, ↑CXCL1, ↑CXCL2, ↑NFKB1, ↑NFKB1A, ↓PYCARD, ↑TNF | 9 | 1.89E-07 |
2) Cell death of immune cells (decreased) | ↓B2M, ↓BCL2, ↑CCL2, ↑CCL5, ↓CIITA, ↑CXCL1, ↑CXCL2, ↓MAPK1, ↑NFKB1, ↑NFKB1A, ↓PEA15, ↓PYCARD, ↑RIPK2, ↓TAB2, ↑TNF, ↓TXNIP | 16 | 4.50E-10 |
2a. Macrophage cell death (decreased) | ↓BCL2, ↑CCL2, ↑CCL5, ↑CXCL1, ↑CXCL2, ↑NFKB1, ↑NFKB1A, ↓PYCARD, ↑TNF | 9 | 3.78E-13 |
Toxicity analysis | |||
Decreases MPT, mitoChondrial swelling | ↓B2M, ↓BCL2, ↑NFKB1, ↓PYCARD, ↑TNF | 5 | 7.27E-08 |
T. cruzi infection of THP-1 mφs vs control (3 h + ATP) | |||
Top biological and molecular functions | |||
1) Inflammatory responses/infection | ↓BCL2, ↑CCL2, ↑CCL5, ↑CXCL1, ↑CXCL2, ↓IL1B, ↓IRF1,↑NFKB1, ↑NFKB1A, ↓NLRP3, ↑PTGS2, ↓PYCARD, ↑RIPK2,↑TNF, ↓TXNIP | 16 | 7.54E-14–1.79E-05 |
1a. Recruitment/migration of phagoCytes/neutrophils | ↑CCL2, ↑CCL5, ↑CXCL1, ↑CXCL2, ↓IL1B, ↑MAPK3, ↑NLRP3, ↓PYCARD, ↑RIPK2, ↑TNF | 9 | 7.69E-09 |
1b. Activation of lymphoCyte/leukoCytes | ↓BCL2, ↑CCL2, ↑CCL5, ↑CXCL1, ↓IL1B, ↓IRF1, ↑NFKB1, ↑PTGS2, ↓PYCARD, ↑RIPK2 ↑TNF, ↓TXNIP | 12 | 3.44E-12 |
2) Cell death of immune cells/necrosis (decreased) | ↓BCL2, ↑CCL2, ↑CCL5, ↑CXCL1, ↑CXCL2, ↓IL1B, ↓IRF1, ↑MAPK3, ↑NFKB1, ↑NFKB1A, ↑NLRP3, ↑PTGS2, ↓PYCARD, ↑RIPK2, ↑TNF, ↓TXNIP | 16 | 9.06E-17–1.99E-05 |
2a. Cell death of phagoCytes, myeloid cells (decreased) | ↓BCL2, ↑CCL2, ↑CCL5, ↑CXCL1, ↑CXCL2, ↓IL1B, ↓IRF1, ↑NFKB1, ↑NFKB1A, ↓PYCARD, ↑TNF | 11 | 9.06E-17 |
Toxicity analysis | |||
Decreased MPT, mitoChondrial swelling | ↓B2M, ↓BCL2, ↑NFKB1, ↓PYCARD, ↑TNF | 5 | 7.27E-08 |
T. cruzi infection of THP-1 mφs vs control (18 h) | |||
Top biological and molecular functions | |||
1) Cell death of immune cells (decreased) | ↓ACTB, ↓CASP4, ↑CCL2, ↑CCL5, ↑CFLAR, ↓CTSB, ↑CXCL1, ↑CXCL2, ↓GAPDH, ↓HSP90AA1, ↓HSP90B1, ↑ IL1B, ↑IRAK1, ↓MAP3K7, ↓MAPK1, ↓MAPK3, ↓NAIP, ↑P2RX7, ↓PEA15, ↓PYCARD, ↓TAB2, ↑TNF, ↓TNFS14, ↓TRAF6 | 24 | 1.48E-12–2.60E-04 |
1a.Cell death of myeloid/phagoCytes | ↓CASP4, ↑CCL2, ↑CCL5, ↑CFLAR, ↑CXCL1, ↑CXCL2, ↑ IL1B, ↑P2RX7, ↓PYCARD, ↑TNF | 10 | 1.72E-12 |
2) Inflammation/infectious disease | ↓CASP4, ↑CCL2, ↑CCL5, ↑CXCL1, ↑CXCL2, ↓HSP90AA1, ↑ IL1B, ↓MAPK1, ↓PANX1, ↑P2RX7, ↓PYCARD, ↑TNF, ↓TNFS14, ↓TRAF6 | 14 | 1.08E-06 |
2a. Activation of leukoCyte/lymphoCytes | ↑CCL2, ↑CCL5, ↑CXCL1, ↓HSP90B1, ↓IL1B, ↓MAP3K7, ↓PYCARD, ↑TNF, ↓TNFS14 | 9 | 2.95E-07 |
2b. Migration of phagoCytes/neutrophils | ↑CCL2, ↑CCL5, ↓CTSB,↑CXCL1, ↑CXCL2, ↑IL1B, ↑P2RX7, ↑TNF | 8 | 2. 07E-07 |
Toxicity analysis | |||
Gene regulation by PPARα | ↓HSP90AA1, ↑IL1B, ↓MAP3K7, ↓MAPK1, ↓MAPK3, ↑TNF, ↓TRAF | 7 | 4.16E-10 |
T. cruzi infection of THP-1 mφs vs control (18 h + ATP) | |||
Top biological and molecular functions | |||
1) Cell death (decreased) | ↓ACTB, ↓B2M, ↓CASP4, ↑CCL2, ↑CCL5, ↓CHUK, ↓CTSB,↑CXCL1, ↑CXCL2,↓GAPDH, ↓HSP90AA1, ↓HS90B1, ↑IRAK1, ↑IRF1, ↓MAP3K7, ↓MAPK1 ↓MAPK12, ↑NFKB1A, ↑P2RX7, ↓PEA15, ↑PTGS2, ↓PYCARD, ↓TAB2, ↑TNF, ↓TNFS14, ↓TRAF6 | 26 | 6.53E-12–4.09E-04 |
1a.Cell death of myeloid/phagoCytes | ↓CASP4, ↑CCL2, ↑CCL5, ↑CFLAR, ↑CXCL1, ↑CXCL2, ↑ IL1B, ↑P2RX7, ↓PYCARD, ↑TNF | 10 | 1.48E-12 |
2) Inflammation/Infectious disease | ↓ACTB, ↓B2M, ↓CASP4, ↑CCL2, ↑CCL5,↓CHUK, ↓CTSB, ↑CXCL1, ↑CXCL2, ↓HSP90B1, ↑IRAK1 ↓MAP3K7, ↑NFKB1A, ↑PTGS2, ↑P2RX7, ↓PYCARD, ↓TIRAP, ↑TNF, ↓TNFS14, ↓TRAF6 | 21 | 3.33E-10–4.43E-04 |
2a. Activation of leukoCyte/lymphoCytes | ↓B2M, ↑CCL2, ↑CCL5, ↑CXCL1, ↑CXCL2, ↓MAP3K7, ↑TNF | 7 | 9.31E-06 |
2b. Migration of phagoCytes/neutrophils | ↑CCL2, ↑CCL5, ↓CHUK, ↓CTSB, ↑CXCL1, ↑TNF ↑CXCL2, ↑NFKB1A, ↑P2RX7, ↑PTGS2, ↓TIRAP | 11 | 2.43E-04 |
Toxicity analysis | |||
Gene regulation by PPARα | ↓CHUK, ↓HSP90AA1, ↓MAP3K7, ↓MAPK1, ↓MAP3K7, ↑NFKB1A, ↑PTGS2, ↑TNF, TRAF6 | 9 | 2.11E-11 |
All differentially expressed proteins identified in THP-1 macrophages infected with T. cruzi for 3 or 18 h (±ATP) (listed in Table 1) were uploaded into Ingenuity Pathway Analysis (IPA) to interpret datasets in the context of biological proCesses and function, and pathway and molecular networks. Presented are the top networks with a p value <0.01 to which maximal number of the differentially expressed proteins identified in chagasic plasma (bolded letters) were assoCiated with. FoCus molecules are the number of differentially expressed plasma proteins assoCiated with an individual network.