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. 2014 Nov 5;9(11):e111539. doi: 10.1371/journal.pone.0111539

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.