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

Jain, R and Dey, B and Khera, A and Srivatsav, P and Gupta, U D and Katoch, V M and Ramanathan, V D and Tyagi, A K (2011) Over-expression of superoxide dismutase obliterates the protective effect of BCG against tuberculosis by modulating innate and adaptive immune responses. Vaccine, 29 (45). pp. 8118-8125. ISSN 0264-410X

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Abstract

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� and increased IL10 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.

Affiliation:	ICMR-National Institute for Research in Tuberculosis
Item Type:	Article
Uncontrolled Keywords:	superoxide, dismutase obliterates, BCG, tuberculosis, innate and adaptive immune responses
Subjects:	Tuberculosis > Laboratory Research > Pathological
Divisions:	Basic Science Research > Clinical Pathology
Depositing User:	Dr. Rathinasabapati R
Date Deposited:	22 Jun 2022 05:13
Last Modified:	07 Feb 2023 09:58
URI:	http://eprints.nirt.res.in/id/eprint/1119

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