Over-expression of superoxide dismutase obliterates the protective effect of BCG against tuberculosis by modulating innate and adaptive immune responses

被引：21

作者：

Jain, Ruchi ^{[1
]}

Dey, Bappaditya ^{[1
]}

Khera, Aparna ^{[1
]}

Srivastav, Priyadarshani ^{[1
]}

Gupta, Umesh D. ^{[2
]}

Katoch, V. M. ^{[2
]}

Ramanathan, V. D. ^{[3
]}

Tyagi, Anil K. ^{[1
]}

机构：

[1] Univ Delhi S Campus, Dept Biochem, New Delhi 110021, India

[2] Natl JALMA Inst Leprosy & Other Mycobacterial Dis, Agra 282001, Uttar Pradesh, India

[3] TB Res Ctr, Dept Clin Pathol, Madras 600031, Tamil Nadu, India

来源：

VACCINE | 2011年 / 29卷 / 45期

关键词：

Tuberculosis; Vaccine; Recombinant; BCG; SOD; Multi-functional T cells; CD4; T-CELLS; MYCOBACTERIUM-TUBERCULOSIS; REACTIVE OXYGEN; ANTIGEN PRESENTATION; VACCINE DESIGN; MEMORY; MODEL; IMMUNOGENICITY; IMMUNOLOGY; INFECTION;

D O I：

10.1016/j.vaccine.2011.08.029

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

An efficient global control of tuberculosis requires development of alternative vaccination strategies that can enhance the efficacy of existing BCG vaccine. In this study, we evaluated the protective efficacy of a recombinant BCG (rBCG) vaccine over-expressing iron-cofactored superoxide dismutase (SOD-A), one of the prominent oxidative stress response proteins of Mycobacterium tuberculosis. Contrary to our expectations, over-expression of SOD-A resulted in the abrogation of BCG's ability to confer protection in guinea pig as well as in murine model. Analysis of immune responses revealed that over-expression of SOD-A by rBCG has pleiotropic effects on innate and adaptive immune responses. Macrophages infected in vitro with rBCG exhibited a marked reduction in apoptosis and microbicidal potential. In addition, rBCG vaccination of mice resulted in a reduced IFN gamma and increased MO production when compared with the BCG vaccination. Further, we show that rBCG vaccination failed to generate an effective multi-functional CD4 T cell response. Altogether, our findings suggest that over-expression of SOD-A in BCG enhances the immuno-suppressive properties of BCG, characterized by skewing of immune responses towards Th2 type, an inefficient multi-functional T cell response and reduced apoptosis and microbicidal potential of macrophages leading to abolishment of BCG's protective efficacy. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：8118 / 8125

页数：8

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