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Macrophage Immune Response Suppression by Recombinant Mycobacterium tuberculosis Antigens, the ESAT-6, CFP-10, and ESAT-6/CFP-10 Fusion Proteins

Document Type : Original Article(s)

Authors

1 Recombinant Protein Laboratory, Biochemistry Department, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran; and Histomorphometry and Stereology Research Center, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran

2 Recombinant Protein Laboratory, Biochemistry Department, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran; and Department of Biochemistry, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran

3 Recombinant Protein Laboratory, Biochemistry Department, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran;

4 Recombinant Protein Laboratory, Biochemistry Department, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran; and Maternal-Fetal Medicine Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract

Background: Macrophage immune responses are affected by the secretory proteins of Mycobacterium tuberculosis (Mtb). This study aimed to examine the immune responses of macrophages to Mtb secretory antigens, namely ESAT-6, CFP-10, and ESAT-6/CFP-10.Methods: THP-1 cells (a human monocytic cell line) were cultured and differentiated to macrophages by phorbol 12-myristate 13-acetate. The cytotoxicity of the recombinant Mtb proteins was assessed using the MTT assay. Two important immune responses of macrophages, namely NO and ROS production, were measured in response to the ESAT-6, CFP-10, and ESAT-6/CFP-10 antigens. The data were analyzed using one-way ANOVA with SPSS, version 16, and considered significant at P<0.05.Results: The results showed that the ESAT-6, CFP-10, and ESAT-6/CFP-10 proteins markedly reduced macrophage immune response. The treatment of the THP-1-differentiated cells with ESAT-6, CFP-10, and ESAT-6/CFP-10 reduced NO and ROS production. The treated THP-1-differentiated cells exhibited less inducible NO synthase activity than did the untreated cells. No toxic effect on macrophage viability was observed for the applied proteins at the different concentrations. Conclusion: It seems that the decline in macrophage immune response is due to the suppression of NO and ROS production pathways without any effect on cell viability.

Keywords

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Iranian Journal of Medical Sciences
Volume 41, Issue 4 - Serial Number 4
79
July 2016
Pages 296-304
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History
  • Received: 02 January 2016
  • Revised: 24 November 2024
  • Accepted: 24 December 2018
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