Epstein-Barr virus-induced gene 3 (EBI3) polymorphisms and expression are associated with susceptibility to pulmonary tuberculosis.
Tuberculosis (TB) remains a major global health problem and host genetic factors play a critical role in susceptibility and resistance to TB. The aim of this study was to identify novel candidate genes associated with TB susceptibility. We performed a population-based case-control study to genotype 13 tag SNPs spanning Epstein-Barr virus-induced gene 3 (EBI3), colony stimulating factor 2 (CSF2), IL-4, interferon beta 1 (IFNB1), chemokine (C-X-C motif) ligand 14 (CXCL14) and myeloid differentiation primary response gene 88 (Myd88) genes in 435 pulmonary TB patients and 375 health donors from China. We observed that EBI3 gene rs4740 polymorphism was associated with susceptibility to pulmonary tuberculosis (PTB) and the allele G was associated with a protective effect against PTB. Furthermore, EBI3 deficiency led to reduced bacterial burden and histopathological impairment in the lung of mice infected with Mycobacterium bovis BCG. Meanwhile, higher abundance of EBI3 was observed in the granuloma of PTB patients and in the lung tissue of BCG-infected mice. Of note, the expression of EBI3 in macrophages was remarkably induced by mycobacteria infection at both mRNA and protein level. In conclusion, EBI3 gene rs4740 polymorphism is closely associated with susceptibility to PTB and the elevation and enrichment of EBI3 in the lung which at least partially derived from macrophages may contribute to the exacerbation of mycobacterial infection.
Clinic and Research Center of Tuberculosis, Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China. Electronic address: zhruijuan923@126.com.
Ruijuan
R
Zheng
Clinic and Research Center of Tuberculosis, Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China; Clinical Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address: haipengliu2013@163.com.
Haipeng
H
Liu
Department of Microbiology and Immunology, Tongji University School of Medicine, Shanghai, China. Electronic address: 731705125@qq.com.
Peng
P
Song
Clinic and Research Center of Tuberculosis, Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China. Electronic address: feng_yonghong@hotmail.com.
Yonghong
Y
Feng
Clinic and Research Center of Tuberculosis, Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China. Electronic address: lianhuaq1013@163.com.
Lianhua
L
Qin
Clinic and Research Center of Tuberculosis, Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China. Electronic address: huangxiaochen.1001@163.com.
Xiaochen
X
Huang
Clinic and Research Center of Tuberculosis, Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China; Clinical Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address: jxchen01@sibs.ac.cn.
Jianxia
J
Chen
Clinic and Research Center of Tuberculosis, Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China. Electronic address: yanghua97065@163.com.
Hua
H
Yang
Clinic and Research Center of Tuberculosis, Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China. Electronic address: nllzh@126.com.
Zhonghua
Z
Liu
Clinic and Research Center of Tuberculosis, Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China. Electronic address: cuizhenling@163.com.
Zhenglin
Z
Cui
Clinic and Research Center of Tuberculosis, Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China. Electronic address: shhuzy@163.com.
Zhongyi
Z
Hu
Clinic and Research Center of Tuberculosis, Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China; Clinical Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address: baoxue_ge@tongji.edu.cn.
Baoxue
B
Ge
D000818:Animals; D058491:Bacterial Load; D016022:Case-Control Studies; D002460:Cell Line; D002681:China; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D054884:Host-Pathogen Interactions; D006801:Humans; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism; D008168:Lung / Q000378:metabolism* / Q000382:microbiology; D008264:Macrophages / Q000382:microbiology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015778:Minor Histocompatibility Antigens; D009163:Mycobacterium bovis / Q000472:pathogenicity; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D065840:Protective Factors; D018121:Receptors, Cytokine / Q000172:deficiency / Q000235:genetics*; D012307:Risk Factors; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control
C097732:EBI3 protein, human; C499601:Ebi3 protein, mouse; D007378:Interleukins; D015778:Minor Histocompatibility Antigens; D018121:Receptors, Cytokine
EBI3; Expression; Mycobacterium tuberculosis; Polymorphism