title: Immune gene networks of mycobacterial vaccine-elicited cellular responses and immunity.
abstract: Gene networks of protective lymphocytes after immune activation with live attenuated vaccines remain poorly characterized. Because Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccine can confer protection against fatal forms of tuberculosis in humans and monkeys, we made use of macaque models to optimally study immune gene networks after BCG vaccination/infection. We first established and validated a large-scale real-time quantitation system and then used it to measure expression levels of 138 immune genes after BCG vaccination/infection of rhesus macaques. Systemic BCG vaccination induced up to 600-fold increases in expression of 78 immune genes among the 138 genes tested at the time when BCG-elicited T cell responses and immunity were apparent. These up-regulated transcripts constituted multiple gene networks that were linked to various aspects of immune function. Surprisingly, the up-regulation of most of these immune genes in the gene networks occurred at 1 week and was sustained at > or = 6 weeks after BCG vaccination/infection. Although early activation of immune gene networks was an immune correlate of anti-BCG immunity, prolonged up-regulation of these networks coincided with the development of vaccine-elicited T cell responses after BCG vaccination/infection. These findings provide molecular evidence suggesting that the BCG-induced gene networks may represent global transcriptomes and proteomes underlying the development of T cell responses and, ultimately, immunity to mycobacteria.
authors.affiliation: Department of Microbiology and Immunology, Center for Primate Biomedical Research, University of Illinois at Chicago, IL, 60612, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Huang
authors.forename: Liyou
authors.initials: L
authors.lastname: Qiu
authors.forename: Richard
authors.initials: R
authors.lastname: Wang
authors.forename: Xioamin
authors.initials: X
authors.lastname: Lai
authors.forename: George
authors.initials: G
authors.lastname: Du
authors.forename: Probhat
authors.initials: P
authors.lastname: Seghal
authors.forename: Yun
authors.initials: Y
authors.lastname: Shen
authors.forename: Lingyun
authors.initials: L
authors.lastname: Shao
authors.forename: Lisa
authors.initials: L
authors.lastname: Halliday
authors.forename: Jeff
authors.initials: J
authors.lastname: Fortman
authors.forename: Ling
authors.initials: L
authors.lastname: Shen
authors.forename: Norman L
authors.initials: NL
authors.lastname: Letvin
authors.forename: Zheng W
authors.initials: ZW
authors.lastname: Chen
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000942:Antigens, Bacterial / Q000008:administration & dosage; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology*; D007111:Immunity, Cellular; D008251:Macaca; D009164:Mycobacterium Infections / Q000276:immunology / Q000517:prevention & control; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000254:growth & development / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001500:BCG Vaccine