Table 3.

The top 20 significantly downregulated DE genes in the TB model versus normal group and their changes in various ag85a/b DNA versus TB model group.

Genbank accession	Gene symbol	Fold Change values of the DE genes									Annotation
		TB model group versus Normal group	DNA IM group versus TB model group				DNA EP group versus TB model group
			10 μg	50 μg	100 μg	200 μg	10 μg	50 μg	100 μg	200 μg
NM_011359	Sftpc	167↓	NO	NO	559↑	395↑	255↑	289↑	565↑	280↑	Surfactant protein C (SFTPC), a hydrophobic protein secreted by alveolar epithelial cells, maintains lung tissue stability by reducing the surface tension of the fluid covering the lungs. 53
NM_001282071	Sftpb	68↓	NO	NO	348↑	253↑	100↑	129↑	207↑	99↑	SFTPB, an amphoteric SFTP secreted by alveolar epithelial cells, increases the diffusion rate and stability of the surfactant layer in vitro. 54
NM_009160	Sftpd	48↓	NO	NO	141↑	60↑	59↑	78↑	146↑	98↑	SFTPD, a member of the collectin family, is soluble innate immune molecule which maintain lung homeostasis through their dual roles as anti‐infectious and immunomodulatory agents. 55 , 56
NM_009349	Inmt	43↓	NO	NO	164↑	154↑	39↑	36↑	223↑	116↑	Indolethylamine N‐methyltransferase, is a methyltransferase that regulates the N‐methylation of tryptamine family proteins, participates in the development and activity of the nervous system. 57
NM_023134	Sftpa1	32↓	NO	NO	127↑	102↑	64↑	50↑	127↑	75↑	SFTPA1, a member of type C lectin subfamily, plays an important role in surfactant homeostasis and defense against respiratory pathogens, and mediates adhesion and phagocytosis of MTB by alveolar macrophages. 58
NM_010329	Pdpn	32↓	NO	NO	57↑	27↑	38↑	66↑	55↑	41↑	Podoplanin, a small transmembrane mucin‐like glycoprotein that plays an important role in immune response. In different inflammation‐related diseases, the expression of Pdpn in immune cells participates in the regulation of inflammation. 59
NM_026323	Wfdc2	32↓	NO	NO	117↑	66↑	53↑	73↑	113↑	70↑	Whey acidic protein four‐disulfide core domain 2, a small secreted protein that functions as a protease inhibitor, plays critical roles in multiple aspects of lung function, such as promoting mucociliary clearance, conferring anti‐inflammatory activity, and reducing surface tension. 60
NM_001029937	Sec1413	28↓	NO	NO	116↑	185↑	83↑	86↑	237↑	139↑	SEC14‐like 3, a 45 kDa secretory protein specifically expressed in airway epithelial cells, has a close relationship with airway inflammation, and decreases significantly with the aggravation of airway inflammation, which may be a new marker of airway inflammation. 61 , 62
NM_001198766	Postn	27↓	NO	NO	87↑	52↑	46↑	79↑	101↑	71↑	Periostin, a 90‐kDa secreted extracellular matrix protein, binds to many extracellular matrix proteins through its different domains, and can bind to diverse integrins to activate the TGF‐β, PI3K/Akt, Wnt, RhoA/ROCK, NF‐κB, MAPK, and JAK pathways. 63
NM_013805	Cldn5	23↓	NO	NO	52↑	28↑	19↑	36↑	66↑	37↑	Claudin‐5, a member of the Claudin family, is an integral membrane protein and a component of tight junctions, which act as physical barriers preventing free passage of solutes and water through the paracellular space between epithelial or endothelial cell sheets.
NM_007817	Cyp2f2	22↓	NO	NO	166↑	209↑	54↑	48↑	314↑	138↑	Cytochrome P450, family 2, subfamily f, polypeptide 2, is a monooxygenase that catalyzes many reactions in drug metabolism and metabolizes a variety of pulmonary toxicants. 64
NM_009701	Aqp5	22↓	NO	NO	31↑	18↑	22↑	25↑	35↑	31↑	Aquaporin 5, a small water channel membrane proteins associated with major intrinsic proteins (p38, MIP etc.), mediates cell migration and proliferation, and participates in inflammatory reaction. 65
NM_007929	Emp2	21↓	NO	NO	64↑	47↑	41↑	45↑	77↑	53↑	Epithelial membrane protein 2, a member of the tetraspan superfamily of membrane protein, has a variety of functions, including endocytosis, cell signaling, proliferation, migration, and adhesion. 66
NM_020509	Retnla	21↓	NO	NO	24↑	NO	27↑	95↑	12↑	18↑	Resistin‐like alpha, a member of the resistin family, is a secreted cysteine‐rich protein with insulin resistance and also an anti‐inflammatory marker of macrophages. 67 , 68
NM_011315	Saa3	20↓	NO	NO	NO	NO	NO	56↑	NO	NO	Serum amyloid A3, a pseudogene in humans, is a major component of acute‐phase inflammation, serves as an endogenous peptide ligand for TLR4, and binds MD‐2 to activate p38 and NF‐κB pathways in a MyD88‐dependent manner. 69
NM_010426	Foxf1	17↓	NO	NO	86↑	68↑	26↑	39↑	124↑	59↑	Forkhead box F1, a mesenchymal transcriptional factor essential for lung development, promotes normal lung homeostasis and repair. 70
NM_008485	Lamc2	17↓	NO	NO	22↑	14↑	23↑	27↑	24↑	19↑	Laminin subunit gamma 2, laminin is an extracellular matrix glycoprotein and the important adhesive component of the epithelial basement membrane. They are involved in various biological processes such as cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. 71
NM_008597	Mgp	17↓	NO	NO	32↑	21↑	26↑	48↑	40↑	27↑	Matrix gla protein, a vitamin K‐dependent inhibitor of calcification, may play an anti‐inflammatory role in monocytes and macrophages. 72
NM_008344	Igfbp6	16↓	NO	NO	58↑	38↑	19↑	15↑	66↑	39↑	Insulin‐like growth factor binding protein 6, prolongs the half‐life of insulin‐like growth factor (IGF), inhibits or stimulates the growth‐promoting effect of IGF in cell culture, activates the MAPK signaling pathway, and induces cell migration  73
NM_010217	Ctgf	15↓	NO	NO	31↑	18↑	25↑	50↑	53↑	44↑	Connective tissue growth factor, a 38‐kDa protein with a tetramodular structure, is involved in the basic lung development process and promotes lung fibroblast proliferation, migration, and differentiation. 74

Abbreviations: DE, differentially expressed; EP, electroporation; IM, intramuscular injection; MTB, Mycobacterium tuberculosis; TB, tuberculosis; ↑, upregulated expression; ↓, downregulated expression.