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© Research
Publication : Scientific reports

Impact of Mycobacterium tuberculosis RD1-locus on human primary dendritic cell immune functions

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Scientific reports - 25 Nov 2015

Etna MP, Giacomini E, Pardini M, Severa M, Bottai D, Cruciani M, Rizzo F, Calogero R, Brosch R, Coccia EM

Link to Pubmed [PMID] – 26602835

Sci Rep 2015 Nov;5:17078

Modern strategies to develop vaccines against Mycobacterium tuberculosis (Mtb) aim to improve the current Bacillus Calmette-Guerin (BCG) vaccine or to attenuate the virulence of Mtb vaccine candidates. In the present study, the impact of wild type or mutated region of difference 1 (RD1) variants on the immunogenicity of Mtb and BCG recombinants was investigated in human primary dendritic cells (DC). A comparative analysis of transcriptome, signalling pathway activation, maturation, apoptosis, cytokine production and capacity to promote Th1 responses demonstrated that DC sense quantitative and qualitative differences in the expression of RD1-encoded factors–ESAT6 and CFP10–within BCG or Mtb backgrounds. Expansion of IFN-γ producing T cells was promoted by BCG::RD1-challenged DC, as compared to their BCG-infected counterparts. Although Mtb recombinants acted as a strong Th-1 promoting stimulus, even with RD1 deletion, the attenuated Mtb strain carrying a C-terminus truncated ESAT-6 elicited a robust Th1 promoting phenotype in DC. Collectively, these studies indicate a necessary but not sufficient role for the RD1 locus in promoting DC immune-regulatory functions. Additional mycobacterial factors are likely required to endow DC with a high Th1 polarizing capacity, a desirable attribute for a successful control of Mtb infection.

https://www.ncbi.nlm.nih.gov/pubmed/26602835