Table 2.
Upregulated genes in intestinal granulomas at 21 days post infection (D21B and D21T, Log2fold>1 in both D21 groups but not in the D7 group).
| Gene | Function | Nematode Host Response | D21 (BOLUS infection)Compared to D7 Bolus | D21 (Trickle infection)Compared to D7 Bolus | |||
|---|---|---|---|---|---|---|---|
| Fold Change | Adjusted p-value | Fold Change | Adjusted p-value | ||||
| Upregulated in both groups compared to D7 | |||||||
| 1 | Cpa3 | Mast cell protease | (125) | 3436.54 | 3.57E-16 | 3296.97 | 5.46E-17 |
| 2 | Fcer1a | High affinity Fc epsilon receptor subunit alpha | (126, 127) | 1643.11 | 4.51E-14 | 1514.01 | 2.21E-14 |
| 3 | Ms4a2 | High affinity Fc epsilon receptor subunit beta | (128) | 784.52 | 5.37E-11 | 534.85 | 1.79E-10 |
| 4 | Trem2 | ECM remodelling | (129) | 324.94 | 5.63E-10 | 199.98 | 7.21E-09 |
| 5 | Cma1 | Mast cell chymase gene | (130) | 187.22 | 2.18E-06 | 133.20 | 4.27E-06 |
| 6 | Igf2 | Hormone similar to insulin (growth factor signalling) |
(131) | 172.14 | 9.10E-08 | 80.95 | 4.01E-06 |
| 7 | Lat | T cell signalling | (132) | 157.93 | 6.03E-05 | 75.62 | 3.57E-04 |
| 8 | Flrt2 | Cell adhesion and/or receptor signalling | (109) | 93.25 | 1.54E-05 | 153.79 | 5.25E-07 |
| 9 | Bcl2 | Regulates cell death | (133) | 86.20 | 3.82E-06 | 75.53 | 4.31E-06 |
| 10 | Tpsb2 | Serine protease. Found in mast cells | (134) | 61.22 | 7.45E-03 | 31.98 | 1.69E-02 |
| 11 | Krba1 | Interferes with transcription | No study found | 60.15 | 3.81E-04 | 69.67 | 1.08E-04 |
| 12 | Selp | Encodes for P-selectin, involved in the recruitment of leukocytes | (135) | 47.34 | 3.76E-04 | 95.26 | 7.84E-06 |
| 13 | Smarcd3 | Regulates transcription through helicase and ATPase activity | No study found | 47.13 | 2.46E-04 | 120.87 | 1.14E-06 |
| 14 | Fgf2 | Basic fibroblast growth factor | (136) | 46.91 | 4.19E-04 | 100.91 | 6.85E-06 |
| 15 | Tlr6 | Innate signalling | (137) | 45.69 | 1.01E-03 | 67.13 | 1.21E-04 |
| 16 | Gata2 | ECM remodeling | (96) | 43.73 | 1.21E-07 | 27.11 | 2.40E-06 |
| 17 | Nmb | Neuropeptide, inhibitor of type-2 inflammation | (138) | 42.68 | 8.41E-03 | 192.35 | 4.21E-05 |
| 18 | Il3ra | Key basophil phenotyping marker | (139) | 38.93 | 3.72E-05 | 31.32 | 6.64E-05 |
| 19 | Kit | Essential for development and survival of mast cells | (140) | 37.61 | 8.43E-11 | 18.76 | 9.65E-08 |
| 20 | Hoxd4 | Homeobox genes, involved in morphogenesis and associated with cancer progression | No study found | 37.54 | 1.38E-02 | 33.98 | 9.81E-03 |
| 21 | Hdac6 | Histone deacetylase 6 involved in transcriptional regulation | (141) | 29.59 | 2.23E-03 | 67.46 | 4.58E-05 |
| 22 | Ccr3 | Chemokine receptor expressed by eosinophils | (142) | 24.46 | 5.06E-04 | 29.93 | 8.32E-05 |
| 23 | Tlr12 | Innate Signalling | (143) | 24.37 | 2.93E-03 | 47.75 | 1.19E-04 |
| 24 | Rgs1 | Regulator of G-protein signaling 1, upregulated in IL-4 and Relmalpha stimulated macrophages | (144) | 23.73 | 3.87E-08 | 27.65 | 2.31E-09 |
| 25 | Msc | Transcriptional repressor that stimulates Th2/Treg responses | No study found | 23.30 | 2.21E-02 | 28.28 | 8.28E-03 |
| 26 | Cdh13 | Cadherin 13, involved in cell growth, survival and proliferation | (145) | 19.68 | 3.43E-02 | 56.39 | 1.20E-03 |
| 27 | Cebpg | Transcription factor, regulates DNA repair | (146) | 15.68 | 2.78E-06 | 16.59 | 5.98E-07 |
| 28 | Adamts12 | Metalloproteinase | No study found | 15.11 | 2.81E-03 | 109.51 | 1.29E-08 |
| 29 | Adamts17 | Metalloproteinase | No study found | 14.80 | 6.53E-04 | 31.18 | 3.28E-06 |
| 30 | Gata3 | Transcription factor, Th2 response | (147) | 13.43 | 2.13E-10 | 17.32 | 1.66E-13 |
| 31 | Ptger2 | Prostaglandin Receptor | (148) | 13.36 | 2.80E-03 | 18.66 | 2.85E-04 |
| 32 | Alox5 | Lipoxygenase, helps metabolise leukotrienes | (149) | 11.93 | 2.02E-08 | 14.08 | 9.29E-11 |
| 33 | Mmp12 | ECM remodeling | (96) | 11.42 | 4.38E-16 | 11.55 | 1.23E-18 |
| 34 | Fgf7 | Fibroblast Growth Factor | No study found | 10.29 | 4.42E-03 | 15.68 | 2.42E-04 |
| 35 | Lif | Inhibits Cell Differentiation | No study found | 9.76 | 2.71E-03 | 17.83 | 3.75E-05 |
| 36 | Flt3 | Cytokine receptor, promotes natural helper cell development | (150) | 8.52 | 2.31E-03 | 8.73 | 1.02E-03 |
| 37 | Lamb2 | Laminin, major component of the basal lamina, associated with collagen networks and regulation of MMPs | No study found | 6.70 | 1.82E-12 | 4.53 | 9.78E-09 |
| 38 | Chil4 | AAM marker Ym2 involved in wound healing | (93) | 6.33 | 1.40E-04 | 6.17 | 4.02E-05 |
| 39 | Chil3 | AAM marker Ym1 involved in wound healing | (20, 87, 95) | 6.23 | 2.02E-08 | 6.17 | 1.30E-09 |
| 40 | Tek | Endothelial-specific receptor tyrosine kinase | No study found | 6.07 | 6.54E-06 | 7.41 | 7.08E-08 |
| 41 | Siglecf | Intestinal eosinophil surface marker | (1) | 6.03 | 4.10E-09 | 8.63 | 1.60E-14 |
| 42 | Adamts2 | Metalloproteinase | No study found | 5.97 | 3.11E-06 | 5.36 | 2.51E-06 |
| 43 | Itgax | Integrin, also known as CD11c | (151) | 5.90 | 9.94E-09 | 5.55 | 4.81E-09 |
| 44 | Retnla | AAM marker, wound healing | (20, 99–101) | 5.25 | 1.02E-12 | 2.99 | 5.07E-07 |
| 45 | Alox15 | Lipoxygenase, helps metabolise leukotrienes | (152) | 5.19 | 2.15E-05 | 4.00 | 1.44E-04 |
| 46 | Sema5a | Involved in lymphocyte activation | (153) | 5.10 | 3.37E-04 | 5.05 | 1.08E-04 |
| 47 | Ccl7 | Chemokine involved in cell migration | (98) | 5.08 | 4.75E-04 | 3.53 | 3.24E-03 |
| 48 | Ccl2 | Cytokine, also known as MCP-1 | (154) | 5.03 | 1.15E-05 | 2.85 | 2.27E-03 |
| 49 | Ptprb | Phosphatase, regulates permeability | (109) | 4.79 | 7.92E-07 | 2.99 | 3.27E-04 |
| 50 | Fn1 | Fibronectin 1, mesenchymal marker | (155) | 4.74 | 6.37E-11 | 3.41 | 2.58E-08 |
| 51 | Rnase2a | Encodes for eosinophil derived cationic proteins and neurotoxins and involved in neutrophil recruitment | (94) | 4.58 | 4.10E-06 | 2.51 | 3.26E-03 |
| 52 | Il1r2 | IL-1 decoy receptor | (119) | 4.44 | 2.54E-05 | 4.00 | 3.50E-05 |
| 53 | Enpp2 | Pyrophosphatase, Also known as autotaxin | (156) | 4.15 | 3.32E-05 | 3.41 | 1.85E-04 |
| 54 | Il1rl1 | IL-33 receptor | (157) | 4.07 | 8.43E-11 | 6.81 | 2.14E-22 |
| 55 | Nfatc1 | Transcription factor | (158) | 4.02 | 9.33E-05 | 2.96 | 1.52E-03 |
| 56 | Alox5ap | Alox5 activating protein | (119) | 4.02 | 3.17E-16 | 4.41 | 3.70E-21 |
| 57 | Btk | Tyrosine kinase | (159) | 3.89 | 6.60E-08 | 3.45 | 1.80E-07 |
| 58 | Cd244 | Natural Killer Cell receptor involved in cell killing also expressed by eosinophils | No study found | 3.88 | 5.10E-15 | 3.19 | 2.34E-12 |
| 59 | Cd163 | M2 macrophage marker | (106) | 3.82 | 7.16E-03 | 3.55 | 4.95E-03 |
| 60 | Hdac5 | Histone deacetylase 5 involved in transcriptional regulation | (141) | 3.71 | 6.87E-09 | 9.97 | 7.84E-30 |
| 61 | Csf2ra | Low affinity receptor for CSF2 | No study found | 3.56 | 1.12E-02 | 4.39 | 8.96E-04 |
| 62 | Timp3 | Tissue inhibitor of metalloproteinase 3 | (160) | 3.53 | 5.51E-17 | 2.02 | 9.41E-07 |
| 63 | Itgb7 | Integrin beta 7 | (161) | 3.41 | 1.91E-02 | 4.23 | 1.87E-03 |
| 64 | Nfatc2 | Transcription factor | (162) | 3.29 | 5.22E-06 | 2.13 | 3.02E-03 |
| 65 | Col15a1 | Collagen | (119) | 3.26 | 6.42E-10 | 3.15 | 9.29E-11 |
| 66 | Vamp2 | Vesicle Associated Membrane Protein 2 | No study found | 3.17 | 8.85E-06 | 2.24 | 9.83E-04 |
| 67 | Tgfbr3 | TGF beta receptor III | (163) | 3.04 | 1.23E-06 | 2.28 | 1.86E-04 |
| 68 | Ctsl | Cathepsin L, lysosomal peptidase | No study found | 2.95 | 4.22E-09 | 2.70 | 5.77E-09 |
| 69 | Adam19 | Metalloproteinase | (104) | 2.80 | 1.38E-05 | 2.99 | 5.38E-07 |
| 70 | Mmp13 | Matrix metalloproteinase | (89) | 2.77 | 6.12E-04 | 4.65 | 8.03E-09 |
| 71 | Igf1 | Hormone similar to insulin (growth factor signalling) |
(84) | 2.77 | 1.24E-02 | 10.58 | 6.71E-12 |
| 72 | Cd34 | Eosinophil adhesion | (164) | 2.74 | 3.83E-07 | 2.33 | 4.91E-06 |
| 73 | Lat2 | Amino Acid Transporter | (165) | 2.73 | 1.49E-10 | 2.13 | 5.34E-07 |
| 74 | Adam8 | Metalloproteinase | (89) | 2.70 | 4.38E-16 | 2.37 | 7.49E-14 |
| 75 | Hpgds | Hematopoietic prostaglandin D synthase | No study found | 2.67 | 2.30E-05 | 4.49 | 5.23E-13 |
| 76 | Vav1 | Vav1 1 oncogene | No study found | 2.57 | 2.13E-05 | 2.47 | 1.04E-05 |
| 77 | Tnc | Extracellular matrix glycoproteins | (166) | 2.48 | 4.22E-09 | 3.97 | 5.08E-23 |
| 78 | Pbx1 | Pre B cell leukemia homeobox 1 | (167) | 2.41 | 2.09E-05 | 2.60 | 5.06E-07 |
| 79 | Icosl | ICOS ligand | (112) | 2.36 | 3.64E-04 | 2.13 | 7.90E-04 |
| 80 | Ctgf | Connective tissue growth factor | (168) | 2.30 | 2.58E-02 | 3.00 | 8.27E-04 |
| 81 | S100a4 | S100 calcium binding protein A4 | No study found | 2.28 | 5.96E-04 | 2.98 | 4.28E-07 |
| 82 | C3 | Complement component | (116) | 2.01 | 4.31E-04 | 2.08 | 4.93E-05 |
| Downregulated in both groups compared to D7 | |||||||
| 1 | Nox1 | Codes for NADPH oxidase 1 | (168) | 10.39 | 2.38E-05 | 6.46 | 2.13E-04 |
| 2 | Ccl2 | Cytokine, also known as MCP-1 | (154) | 5.03 | 1.15E-05 | 2.85 | 2.27E-03 |
| 3 | Ccl7 | Chemokine involved in cell migration | (98) | 5.08 | 4.75E-04 | 3.53 | 3.24E-03 |
| 4 | Ccl28 | Increases the migration of CCR3 expressing eosinophils | (169) | 3.26 | 4.22E-04 | 4.61 | 5.83E-07 |
| 5 | Ccl20 | Implicated in the formation and function of mucosal lymphoid tissues | (168) | 3.12 | 9.80E-04 | 6.06 | 1.31E-08 |
| 6 | Ido1 | involved in tryptophan metabolism | (170) | 2.34 | 9.30E-03 | 2.15 | 9.81E-03 |
| 7 | Pglyrp1 | Pro-inflammatory innate immunity protein found in the granules of eosinophils and macrophages | No study found | 2.16 | 1.83E-08 | 2.36 | 8.51E-12 |
| 8 | Ptgdr | Prostaglandin receptor, involved in the chemotaxis of leukocytes (e.g. eosinophils) | (171) | 2.02 | 7.49E-05 | 9.14 | 1.63E-25 |