title: Dietary zinc deficiency impairs humoral and cellular immune responses to BCG and ESAT-6/CFP-10 vaccination in offspring and adult rats.
abstract: BACKGROUND
  Besides being the world's most widely used vaccine, BCG is the most controversial vaccine in current use. Estimates of protection impaired by BCG against pulmonary TB vary from nil to 80%. Dietary zinc deficiency has been confirmed to impair the immune function of animals. However, knowledge about effects of mild dietary zinc deficiency and the time of vaccination on BCG vaccine responsiveness in offspring and adult rats is limited. This work investigated the consequences of feeding zinc deficient and normal zinc diets to rats during gestation, infancy or adulthood on the immune responses to BCG vaccination.
  
  
  METHODS
  On gestation day 0, sixteen maternal rats were divided into two groups and fed with diets bellow: a control diet ad libitum (30 μg zinc/g diet, NC), a zinc deficient diet ad libitum (8 μg zinc/g diet, ZnD). Pup rats were served as experimental subjects. From day 1 of pregnancy upon delivery, maternal rats were given a standard diet (30 mg/kg/day zinc) or zinc deficient diet (8 mg/kg/day zinc) respectively. Adult male 10-week Wistar rats were divided into two dietary groups for 17 weeks of feeding: a control diet ad libitum (30 μg zinc/g diet, NC), a zinc deficient diet ad libitum (8 μg zinc/g diet, ZnD). The birth time of newborn pups was recorded as the zero week. For adult male rats, the time of receiving different assigned diet was recorded as the zeroth week. Newborn pups of these maternal rats were immunized with BCG vaccine or MTB antigen ESAT-6/CFP-10 at postnatal 0 and 2 week. The adult male rats were immunized on the 12th and 14th week. Then, blood samples, thymus and spleen from the rats were harvested for detection of humoral and cell-mediated immune responses using ELISA, MTT and QRT-PCR analysis. Decreased INF-γ and TNF-α production in plasma, changes of expression level of ZIP2, ZIP8, NF-κB and IL-6 mRNA in immune organs, together with reduced T cell proliferation was observed in pups and adult BCG rats suffered from dietary zinc deficiency. Small differences were observed between rats received BCG vaccine and MTB antigen ESAT-6/CFP-10.
  
  
  RESULTS
  Our data clearly indicate that dietary zinc deficiency can weaken the plasma cytokine levels and cell-mediated responses to BCG and ESAT-6/CFP-10 vaccine via decreasing T cell proliferation, down-regulating INF-γ and TNF-α production and affecting the expression of ZIP2, ZIP8, NF-κB and IL-6 mRNA. In addition, the vaccine immunogenicity of BCG and ESAT-6/CFP-10 was not significantly affected by the time of vaccination.
authors.affiliation: Departmnet of Biochemistry and Molecular Biology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Shi
authors.affiliation: Departmnet of Biochemistry and Molecular Biology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, China. Electronic address: zhanglianying@sdu.edu.cn.
authors.forename: Lianying
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Departmnet of Biochemistry and Molecular Biology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, China.
authors.forename: Changcai
authors.initials: C
authors.lastname: Li
authors.affiliation: Departmnet of Biochemistry and Molecular Biology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Hu
authors.affiliation: Shandong Provincial Chest Hospital, Jinan, Shandong, China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Shandong Provincial Chest Hospital, Jinan, Shandong, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Departmnet of Pathology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, China.
authors.forename: Gengyin
authors.initials: G
authors.lastname: Zhou
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood / Q000235:genetics; D003677:Deficiency Diseases / Q000097:blood / Q000235:genetics / Q000276:immunology*; D004032:Diet; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D005865:Gestational Age; D007111:Immunity, Cellular / Q000187:drug effects* / Q000235:genetics; D056724:Immunity, Humoral / Q000187:drug effects* / Q000235:genetics; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology*; D013154:Spleen / Q000276:immunology / Q000382:microbiology; D013601:T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D013950:Thymus Gland / Q000276:immunology / Q000382:microbiology; D014611:Vaccination; D015032:Zinc / Q000172:deficiency*
chemical_list: D001500:BCG Vaccine; D016207:Cytokines; C505464:ESAT-6-CFP10 fusion protein; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D015032:Zinc
keywords: BCG; ESAT-6/CFP-10; ZIP2; ZIP8