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Clinical and Vaccine Immunology, July 2009, p. 991-998, Vol. 16, No. 7
1071-412X/09/$08.00+0 doi:10.1128/CVI.00091-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Differential Live Mycobacterium tuberculosis-, M. bovis BCG-, Recombinant ESAT6-, and Culture Filtrate Protein 10-Induced Immunity in Tuberculosis
Zahra Hasan,1*
Bushra Jamil,1,2
Mussarat Ashraf,1
Muniba Islam,1
Maqboola Dojki,1
Muhammad Irfan,2 and
Rabia Hussain1
Department of Pathology and Microbiology,1 Department of Medicine, The Aga Khan University, Karachi, Pakistan2
Received 2 March 2009/ Returned for modification 5 April 2009/ Accepted 4 May 2009
The high prevalence of Mycobacterium tuberculosis makes it imperative that immune responses to evaluate could be predictive of infection. We investigated live Mycobacterium- and recombinant antigen-induced cytokine and chemokine responses in patients with active tuberculosis (TB) compared with those of healthy controls from an area where TB is endemic (ECs). M. tuberculosis-, M. bovis BCG-, ESAT6-, and culture filtrate protein 10 (CFP10)-induced responses were determined in peripheral blood mononuclear cells from patients with pulmonary TB (n = 38) and ECs (n = 39). The levels of the cytokines gamma interferon (IFN-
) and interleukin-10 (IL-10) and the chemokines CCL2, CCL3, and CXCL9 were measured. The levels of M. tuberculosis- and BCG-induced IFN- secretion were significantly reduced (P = 0.002 and P < 0.01, respectively), while the amount of IL-10 induced by both virulent (P < 0.01) and avirulent (P = 0.002) mycobacteria was increased in patients with TB. The ESAT6-induced IFN- responses were increased in the patients with TB (P = 0.013) compared with those in the EC group. When tuberculin skin test (TST)-negative (TST–; induration, <10 mm) and TST-positive (TST+) donors were studied separately, both TST– and TST+ individuals showed increased IFN- responses to M. tuberculosis compared with the responses of the patients with TB (P = 0.037 and P = 0.006, respectively). However, only TST+ ECs showed reduced IFN- responses to ESAT6 (P = 0.008) compared with the responses of the patients with TB. The levels of M. tuberculosis-induced CCL2 (P = 0.006) and CXCL9 (P = 0.017) were greater in the patients with TB. The levels of CCL3 secretion in response to Mycobacterium and antigen stimulation were comparable between the two groups. While the levels of ESAT6-induced chemokines did not differ between the patients with TB and the ECs, the levels of CFP10-induced CCL2 (P = 0.01) and CXCL9 (P = 0.001) were increased in the patients. These data indicate differential host IFN-, CXCL9, and CCL2 responses to live mycobacteria and mycobacterial antigens and have implications for the identification of potential biomarkers of infection which could be used for the diagnosis of TB.
* Corresponding author. Mailing address: Department of Pathology and Microbiology, P.O. Box 3500, Aga Khan University, Stadium Road, Karachi 74800, Pakistan. Phone: 92 21 486 4511. Fax: 92 21 493 2494. E-mail: zahra.hasan{at}aku.edu
Published ahead of print on 13 May 2009.
Clinical and Vaccine Immunology, July 2009, p. 991-998, Vol. 16, No. 7
1071-412X/09/$08.00+0 doi:10.1128/CVI.00091-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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