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A recombinant Mycobacterium smegmatis induces potent bactericidal immunity against Mycobacterium tuberculosis.

Abstract：

:We report the involvement of an evolutionarily conserved set of mycobacterial genes, the esx-3 region, in evasion of bacterial killing by innate immunity. Whereas high-dose intravenous infections of mice with the rapidly growing mycobacterial species Mycobacterium smegmatis bearing an intact esx-3 locus were rapidly lethal, infection with an M. smegmatis Δesx-3 mutant (here designated as the IKE strain) was controlled and cleared by a MyD88-dependent bactericidal immune response. Introduction of the orthologous Mycobacterium tuberculosis esx-3 genes into the IKE strain resulted in a strain, designated IKEPLUS, that remained susceptible to innate immune killing and was highly attenuated in mice but had a marked ability to stimulate bactericidal immunity against challenge with virulent M. tuberculosis. Analysis of these adaptive immune responses indicated that the highly protective bactericidal immunity elicited by IKEPLUS was dependent on CD4(+) memory T cells and involved a distinct shift in the pattern of cytokine responses by CD4(+) cells. Our results establish a role for the esx-3 locus in promoting mycobacterial virulence and also identify the IKE strain as a potentially powerful candidate vaccine vector for eliciting protective immunity to M. tuberculosis.

journal_name

Nat Med

journal_title

Nature medicine

authors

Sweeney KA,Dao DN,Goldberg MF,Hsu T,Venkataswamy MM,Henao-Tamayo M,Ordway D,Sellers RS,Jain P,Chen B,Chen M,Kim J,Lukose R,Chan J,Orme IM,Porcelli SA,Jacobs WR Jr

doi

10.1038/nm.2420

subject

Has Abstract

pub_date

2011-09-04 00:00:00

pages

1261-8

issue

10

eissn

1078-8956

issn

1546-170X

pii

nm.2420

journal_volume

17

pub_type

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