Pattern recognition and cellular immune responses to novel Mycobacterium tuberculosis-antigens in individuals from Belarus

Ahmed, Raija K and Rohava, Zoyia and Balaji, Kithiganahalli N and Hoffner, Sven E and Gaines, Hans and Magalhaes, Isabelle and Zumla, Alimuddin and Skrahina, Alena and Maeurer, Markus J (2012) Pattern recognition and cellular immune responses to novel Mycobacterium tuberculosis-antigens in individuals from Belarus. In: BMC Infectious Diseases, 12 .

PDF Pattern.pdf - Published Version Restricted to Registered users only Download (798kB) | Request a copy

Abstract

Background: Tuberculosis (TB) is an enduring health problem worldwide and the emerging threat of multidrug resistant (MDR) TB and extensively drug resistant (XDR) TB is of particular concern. A better understanding of biomarkers associated with TB will aid to guide the development of better targets for TB diagnosis and for the development of improved TB vaccines. Methods: Recombinant proteins (n = 7) and peptide pools (n = 14) from M. tuberculosis (M.tb) antigens associated with M.tb pathogenicity, modification of cell lipids or cellular metabolism, were used to compare T cell immune responses defined by IFN-gamma production using a whole blood assay (WBA) from i) patients with TB, ii) individuals recovered from TB and iii) individuals exposed to TB without evidence of clinical TB infection from Minsk, Belarus. Results: We identified differences in M.tb target peptide recognition between the test groups, i.e. a frequent recognition of antigens associated with lipid metabolism, e.g. cyclopropane fatty acyl phospholipid synthase. The pattern of peptide recognition was broader in blood from healthy individuals and those recovered from TB as compared to individuals suffering from pulmonary TB. Detection of biologically relevant M.tb targets was confirmed by staining for intracellular cytokines (IL-2, TNF-alpha and IFN-gamma) in T cells from non-human primates (NHPs) after BCG vaccination. Conclusions: PBMCs from healthy individuals and those recovered from TB recognized a broader spectrum of M.tb antigens as compared to patients with TB. The nature of the pattern recognition of a broad panel of M.tb antigens will devise better strategies to identify improved diagnostics gauging previous exposure to M.tb; it may also guide the development of improved TB-vaccines.

Item Type:	Journal Article
Publication:	BMC Infectious Diseases
Publisher:	BioMed Central
Additional Information:	Copyright of this article belongs to BioMed Central.
Department/Centre:	Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited:	18 Apr 2012 05:22
Last Modified:	11 Jan 2013 11:09
URI:	http://eprints.iisc.ac.in/id/eprint/44311

Actions (login required)

View Item