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Open Access Research article

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

Raija K Ahmed1, Zoyia Rohava2, Kithiganahalli N Balaji3, Sven E Hoffner1, Hans Gaines1, Isabelle Magalhaes4, Alimuddin Zumla5, Alena Skrahina2 and Markus J Maeurer46*

Author Affiliations

1 Swedish Institute for Communicable Disease Control (SMI), Solna, Sweden

2 Republican Scientific and Practical Center for Pulmonology and Tuberculosis, Minsk, Belarus

3 Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India

4 Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Nobelsväg 16, SE 17182 Solna, Sweden

5 Department of Infection, University College London Medical School, Windeyer Institute of Medical Sciences, London, UK

6 Center for allogeneic stem cell transplantation (CAST), Karolinska Hospital, Stockholm, Sweden

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BMC Infectious Diseases 2012, 12:41  doi:10.1186/1471-2334-12-41

Published: 15 February 2012

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-γ 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-α and IFN-γ) 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.

Keywords:
T-cells; M. tuberculosis; TB; Antigen-recognition; Biomarkers