Temporal changes in the gene signatures of BCG-vaccinated guinea pigs in response to different mycobacterial antigens. 2010

Julia A Tree, and Jyoti Patel, and Ruth E Thom, and Michael J Elmore, and Hubert Schäfer, and Ann Williams, and Philip D Marsh
Health Protection Agency, Centre for Emergency Preparedness and Response, Porton Down, Salisbury, Wiltshire SP4 OJG, UK. julia.tree@hpa.org.uk

Mycobacterium bovis BCG-vaccination in the guinea pig model of tuberculosis (TB) is sufficiently protective that candidate TB vaccines are judged against this. Little is understood about how the BCG vaccine works and, in the absence of a definitive correlate of protection, it is difficult to interpret the significance of novel vaccine induced host responses. Here an extended custom-made microarray (86 guinea pig genes) was used to dissect temporal changes in BCG-vaccine induced gene signatures to different mycobacterial antigens. Initially at 4h, pro-inflammatory genes such as IL-1α, IL-1β, IL-8 and GRO were up-regulated (P<0.001) and these were then superseded by IFN-γ and GM-CSF (at 12 and 20h) post-stimulation, ex vivo with PPD. Similar genes were seen following stimulation with viable BCG but with the addition of IL-23 (P<0.01) after 8h. Our results suggest that temporal changes in the up- and down-regulation of a variety of genes are required to trigger a successful protective response to TB in guinea pigs. This provides base-line information against which new TB vaccines can be compared.

UI MeSH Term Description Entries
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000942 Antigens, Bacterial Substances elaborated by bacteria that have antigenic activity. Bacterial Antigen,Bacterial Antigens,Antigen, Bacterial
D001500 BCG Vaccine An active immunizing agent and a viable avirulent attenuated strain of MYCOBACTERIUM BOVIS, which confers immunity to mycobacterial infections. It is used also in immunotherapy of neoplasms due to its stimulation of antibodies and non-specific immunity. Bacillus Calmette Guerin Vaccine,Calmette Guerin Bacillus Vaccine,Calmette's Vaccine,Calmette Vaccine,Calmettes Vaccine,Vaccine, BCG,Vaccine, Calmette's
D013154 Spleen An encapsulated lymphatic organ through which venous blood filters.
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor
D014376 Tuberculosis Any of the infectious diseases of man and other animals caused by species of MYCOBACTERIUM TUBERCULOSIS. Koch's Disease,Kochs Disease,Mycobacterium tuberculosis Infection,Infection, Mycobacterium tuberculosis,Infections, Mycobacterium tuberculosis,Koch Disease,Mycobacterium tuberculosis Infections,Tuberculoses
D015854 Up-Regulation A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins. Receptor Up-Regulation,Upregulation,Up-Regulation (Physiology),Up Regulation

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