Increased expression of Mycobacterium tuberculosis 19 kDa lipoprotein obliterates the protective efficacy of BCG by polarizing host immune responses to the Th2 subtype
Authors: V D Ramanathan
R Singh
A K Tyagi
H Shakila
N Dhar
M Naseema
C N Paramasivan
A Khera
R Jain
P R Narayanan
V Rao
Journal: Scandinavian journal of immunology (2005)
Discipline: IMMUNOLOGY
Keywords: Mycobacterium tuberculosis; immune effector functions; host-signalling cascades; 19 kDa antigen; interleukin-12
Affiliations: Department of Biochemistry, University of Delhi South Campus, New Delhi, India.

Abstract:  Mycobacterium tuberculosis can not only neutralize immune effector functions, but also has the ability to modulate host-signalling cascades involved in the development of these responses. The 19 kDa antigen (Rv3763), a lipoprotein of M. tuberculosis, elicits high levels of interleukin (IL)-12 from macrophages in addition to its powerful immunomodulatory properties, leading to suppression of antigen-presentation signalling cascades. The present study was aimed at analysing the effect of overexpression of this antigen on the immunostimulatory properties of M. bovis Bacille Calmette-Guerin (BCG). We have constructed a recombinant BCG strain (rBCG19N) producing higher levels of the 19 kDa antigen in both the cytoplasmic (approximately eightfold) and extracellular (approximately fivefold) fractions as compared to the wildtype BCG. Immunization of mice with rBCG19N elicited high levels of interferon-gamma (IFN-gamma) and relatively low levels of IL-10 against the purified 19 kDa antigen. However, in response to total BCG sonicate, mice immunized with rBCG19N produced significantly high levels of IL-10 with relatively very low levels of IFN-gamma. This polarization of the host immune responses towards T-helper 2 subtype resulted in complete abrogation of the protective efficacy of BCG, when rBCG19N was used as a live vaccine against M. tuberculosis challenge in guinea pigs. 

Retracted: No

PubPeer comments:
 Figure 3B. Panels in the top row of the SB (SB431542) treated cells appear to show an overlap with panels in the top row of the ASB10 (SB431542+Activin-A) treated cells. Shown with boxes in two colors green. Could the authors please check? The red color in the right panels appears to be brighter, but the constellation of cells looks very similar.  , 
 The authors of the article entitled, NKX2-1 Activation by SMADS Signaling After Definitive Endoderm Differentiation in Human Embryonic Stem Cell, published in Stem Cells Dev 2013;22;9:1433u20131442 wish to correct errors that appeared in Figure 3.  Original Figure 3 There is an incorrect entry in the images in Figure 3, SB431542 treated cells stained for NKX2.1 and FOXA2, which show a partial overlap with images in the top row of the SB431542+Activin-A panel, also stained for NKX2.1 and FOX A2. The images used in Figure 3 were taken from random images acquired from the same well treated with SB431542+Activin-A with possible partial overlap rather than a well treated with SB431542 and a well treated with SB431542+Activin-A. The authors have supplied a revised Figure 3 as shown next.  The online version of this article has been revised to reflect these corrections. The authors apologize for the mistake; the erroneous image insert did not affect the ultimate conclusion of the manuscript. ,