Immune gene networks of mycobacterial vaccine-elicited cellular responses and immunity.
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.
Huang
Dan
D
Department of Microbiology and Immunology, Center for Primate Biomedical Research, University of Illinois at Chicago, IL, 60612, USA.
Qiu
Liyou
L
Wang
Richard
R
Lai
Xioamin
X
Du
George
G
Seghal
Probhat
P
Shen
Yun
Y
Shao
Lingyun
L
Halliday
Lisa
L
Fortman
Jeff
J
Shen
Ling
L
Letvin
Norman L
NL
Chen
Zheng W
ZW
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*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001500:BCG Vaccine